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OSMANIA UNIVERSITY LIBRARY 

Cal, No. 




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Author 



This booUld be returned on|? r before the date last marked beJ 



ORGANIC SYNTHESES 



THESE VOLUMES NOW READY 



Volume I. 

ROGER ADAMS, University of Illinois, Editor-in- 
Chief. vi+84 pages, 6 by 9; 7 figures Cloth. 

Volume II. 

JAMES BRYANT CONANT, Harvard University, 
Editor-in-Chief, vii-f 100 pages, 6 by 9; 3 figures. 
Cloth. 

Volume III. 

HANS THACHER CLARKE, Columbia University, 
Editor-m-Chief. 4+105 pages, 6 by 9; 3 f.gures. 
Cloth. 

Volume IV. 

OLIVER KAMM, Parke, Davis, and Company, Editor- 
in-Chief, v-f 89 pages, 6 by 9; 3 figures. Cloth. 

Volume V. 

CARL SHIPP MARVEL, University of Illinois, Editor- 
in-Chief 4+ 1 10 pages, 6 by 9; 3 figures. Cloth. 

Volume VI. 

HENRY OILMAN, Iowa State College, Editor-in- 
Chief v+i2o pages; 6 by 9; 5 figures. Cloth. 

Volume VII. 

FRANK C. WHITMORE, Northwestern University, 
Editor-in-Chief, vii-f- 105 pages; 6 by 9; i figure. 
Cloth. 

Volume VIII. 

ROGER ADAMS, University of Illinois, Editor-in- 
Chief, v-f 139 pages; 6 by 9; 3 figures. Cloth. 

Volume IX. 

JAMES BEY ANT CONANT, Harvard jUniversity, 
Editor-in-Chief, vii-f 108 pages, 6 by 9; i figure. 
Cloth. 

Volume X 

HVNS THACHER CLARKE, Columbia University, 
Editor-in-Chief, vii-f 115 pages, 6 by 9; 4 figures. 
Cloth. 



ORGANIC SYNTHESES 

AN ANNUAL PUBLICATION OF SATISFACTORY 

METHODS FOR THE PREPARATION 

OF ORGANIC CHEMICALS 



EDITORIAL BOARD 

OLIVER KAMM, Editor-in-Chief 

ROGER ADAMS J. B. CONANT 

H. T. CLARKE C. S. MARVEL 

F. C. WHITMORE 



W. G. CHRISTIANSEN 
A. W. Dox 
GRAHAM EDGAR 
L. F. FIESER 
HENRY GILMAN 



CONTRIBUTORS 
J. W. HOWARD 
C. D. KURD 

S. M. McELVAIN 

J. F. NORRIS 

J. A. NlEUWLAND 



C. S. PALMER 
PICATINNY ARSENAL 
J. S. REICHERT 
F. K. THAYER 
E. B. VLIET 



VOL. IV. 



NEW YORK 

JOHN WILEY & SONS, INC. 
LONDON: CHAPMAN & HALL, LIMITED 



Copyright, 1925 

BY 
ROGER ADAMS 



All Rights Reserved 
This book or any part thereof must not 
be reproduced in any form mthout 
the written permission of the publisher. 



Printed in U. S. A. 



PRESS OF 
SRAUNWORTH ft CO.. INC. 



BROOKLYN, NEW YORK 



PREFACE TO VOLUME IV 



THE general plan outlined in the first volume of the series 
has been followed in the subsequent publications; but it has 
been found advisable to include preparations which are carried 
out on a somewhat reduced scale, since the carefully described 
directions have found application not merely in the semi- 
commercial preparation of needed research chemicals and 
reagents but also in the instruction of graduate students enter- 
ing the organic field. However, it is the experience of the 
editors that the reduction of preparations described on a large 
scale is usually less difficult than the reverse procedure. 

The sections on " Other Methods of Preparation" are not 
intended to include all possible methods but rather those that 
are of interest chiefly from the preparative standpoint. The 
Cumulative Index, started with Volume III, is being continued. 

The friendly cooperation of other workers in Organic Chem- 
istry has been gratifying, and the editors again cordially invite 
contributions from any investigator who has occasion to study 
an organic preparation exhaustively enough to justify the 
presentation of certified directions. 



ORGANIC SYNTHESES 



ACETYL MANDELYL CHLORIDE 

C 6 H 5 CHOHCO 2 H-f CHaCOCl -> 

C 6 H 5 CH(OCOCH3)CO2H-fHCl 

C 6 H 5 CH(OCOCH3)C02H+SOCl2 -> 

C 6 H 5 CH(OCOCH3)COC1+SO 2 +HC1 

Prepared by F. K. THAYER. 

Checked by ROGER ADAMS and E. E. DREGER. 

1. Procedure 

IN a 500-cc. Claisen distilling flask with a low side-tube 
connected to a condenser, are placed 105 g. of mandelic acid 
(m.p. 118) and 151 g. of acetyl chloride. A reaction sets in 
without the application of heat (Note i). As soon as a clear 
solution results, the flask is warmed on a water bath and the 
excess acetyl chloride is distilled. The last trace of acetyl 
chloride may be removed by prolonged drying in a vacuum. 
The acetyl mandelic acid then crystallizes in large, round, 
white clusters after one or two days' standing. The yield is 
130-133 g. (97-99 per cent of the theoretical amount) (Note 2). 

To the crude acetyl mandelic acid still containing some 
acetyl chloride obtained as described above, is added 250 g. of 
thionyl chloride. The reaction starts at once without warming 
but it is necessary to reflux for four hours to complete the 
reaction (Note 3). The excess thionyl chloride is then distilled 



2 ORGANIC SYNTHESES 

and the residue distilled in a vacuum (Note 4). The yield is 
115-120 g. (79-83 per cent of the theoretical amount) of almost 
colorless liquid boiling at i25-i30/io mm. (i5o-i55/33 mm.). 

2. Notes 

1. Occasionally the application of a little heat is necessary 
to bring about a more rapid acetylation. 

2. The melting points given in the literature range from 
39 to 80. The acetyl mandelic acid is difficult to crystallize 
but may be purified from benzene or chloroform, preferably 
the former. The product thus obtained melts at about 79-80. 

3. Prolonged refluxing of the acetylated mandelic acid with 
the thionyl chloride tends to lower the yield. 

4. Anschiitz gives the boiling point of acetyl mandelyl 
chloride as 129 '/io mm. The vacuum used should be as low 
as possible, to avoid the formation of tar during the distillation. 

3. Other Methods of Preparation 

Acetyl mandelic acid was described by Naquet and Lougui- 
nine, 1 but their product has been shown to be contaminated 
with the ethyl ester of acetyl mandelic acid. Dupont 2 obtained 
the compound by the oxidation of diacetyl i, 4-diphenylbutine- 
2-diol-i, 4. Anschiitz and Bocker 3 prepared acetyl mandelic 
acid, and from it the acid chloride, by the use of phosphorus 
pentachloride, but with poor yields. Von Braun and Mliller 4 
state that acetyl mandelyl chloride can be made from acetylated 
mandelic acid and thionyl chloride, the resulting product being 
a viscous yellow oil. 

1 Compt. rend. 62, 430 (1866); Ann. 139, 302 (1866). 

2 Compt. rend. 150, 1525 (1910). 

3 Ann. 368, 57, 59 (1909). 
4 Ber. 51, 244 (1918). 



II 

a-AMINO-n-CAPROIC ACID 



CH3(CH2J3CHNH2CO 2 H+NH 4 Br 

Prepared by C. S. MARVEL and V. DU VIGNEAUD. 
Checked by H T. CLARKE and E. R. TAYLOR. 



1. Procedure 

IN a i-l. round-bottom flask is placed 760 g. of concentrated 
ammonium hydroxide (sp. gr. 0.9) and to this is slowly added 
150 g. of a-bromocaproic acid (Note i). The flask is well 
stoppered and allowed to stand in a warm place (50-55) for 
twenty to thirty hours. The amino acid separates and is fil- 
tered off with suction and washed with methyl alcohol (Note 2) . 
This crop of crystals weighs 51-56 g. The aqueous filtrate is 
evaporated nearly to dryness on a steam bath and then treated 
with about 250 cc. of methyl alcohol. This precipitates a sec- 
ond crop of amino acid contaminated with ammonium bromide. 
On washing with methyl alcohol and recrystallizing from water, 
there is obtained 10-15 g- niore of pure product. The total 
yield is 63-68 g, (62-67 per cent of the theoretical amount). 



2. Notes 

1. The once-distilled bromocaproic acid (p. 9) is satisfac- 
tory. 

2. If the amino acid is not carefully washed with alcohol, it 
contains ammonium bromide and may possess an objectionable 

3 



ORGANIC SYNTHESES 



odor. Methyl alcohol is preferable to ethyl alcohol since it dis- 
solves ammonium bromide more readily. 



3. Other Methods of Preparation 

a-Amino-w-caproic acid has been prepared by the action of 
ammonia on a-bromo-rc-caproic acid. 1 

1 J. prakt. Chem (2) 1, 7 (1870); Ber. 33, 2381 (1900); Z. physiol. Chem. 86, 
456 (1913); J. Am. Chem. Soc. 42, 320 (1920). 



Ill 

ARSONO- AND ARSENOACETIC ACIDS 

ClCH 2 C0 2 Na+Na 3 As03 -> NaCl + CH 2 (CO 2 Na)AsO3Na 2 
2CH 2 (CO 2 H)As03H 2 +8H(H 3 PO 2 ) - AsCH 2 CO 2 H+6H 2 O 

I! 

AsCHoCOoH 

Prepared by C. S. PALMER. 
Checked by OLIVER KAMM. 

1. Procedure 

ONE HUNDRED grams of powdered arsenious oxide is added to 
the hot solution obtained by dissolving 160 g. of sodium hydrox- 
ide in 300 cc. of water. After the solution has cooled to 20, 
48 g. of chloroacetic acid is added. The suspension is well 
stirred during about five minutes, when a strongly exothermic 
reaction begins, the temperature rises to 70-75, and a clear 
solution results. 

The reaction mixture is permitted to stand at room tempera- 
ture during one hour, or longer if desired (Note i). The solu- 
tion is acidified with 160 cc. of glacial acetic acid and, after the 
temperature has been lowered to 40 by cooling, the precipi- 
tated arsenious oxide is filtered off by suction and washed with 
50 cc. of water. 

The filtrate is poured into a solution containing 185 g. of 
crystallized barium chloride dissolved in 600 cc. of hot water. 
Barium arsonoacetate, Ba(O 2 CCH 2 AsOaBa) 2 (hydrated), forms 
a thick, finely divided precipitate. The mixture is stirred for 
several minutes and then allowed to stand until the following 
day, when it is filtered upon a is-cm. Biichner funnel and washed 

5 



6 ORGANIC SYNTHESES 

thoroughly with water (Note 2). The yield of air-dry * product 
is 220 g. (96 per cent of the theoretical amount). 

Sodium arsonoacetate is prepared by adding the freshly 
filtered and washed barium arsonoacetate as obtained above 
(without drying) to a solution of 108 g. of anhydrous sodium 
sulfate in 500 cc. of hot water. The mixture is mechanically 
stirred for one hour, the barium sulfate filtered off, and the 
filtrate concentrated on the steam bath until crystallization 
commences. Upon cooling and stirring (Note 3), sodium arsono- 
acetate separates and is filtered by suction, the filtrate being 
concentrated to obtain a second crop of crystals. The yield of 
the combined fractions is 100-110 g. (80-88 per cent of the 
theoretical amount). 

A solution of 12.5 g. of sodium arsonoacetate and 30 g. of 
sodium hypophosphite (NaH 2 PO2-HoO) in 150 cc. of cold 15 
per cent sulfuric acid is allowed to stand at room temperature. 
After two or three days, the yellow precipitate is filtered off, 
washed with water, and dried in a vacuum over sulfuric acid or 
phosphorus pentoxide. A second crop is obtained by allowing 
the mother liquid to stand for two days longer. 

The arsenoacetic acid consists of minute yellow needles, 
which do not melt below 260 although they undergo consider- 
able decomposition above 200. The yield is 5 g. (74 per cent 
of the theoretical amount). 



2. Notes 

i. The reaction between sodium arsenite and chloroacetic 
acid is very rapid, as may easily be demonstrated by titrating 
i-cc. portions of the solution with N/io iodine, according to the 
usual volumetric method for arsenious acid, before and after 
the reaction with chloroacetic acid. The excess of sodium 
arsenite is necessary, as was learned by means of an iodometric 
study of the reaction. 

* The air-dry sample contains 13 per cent of water of hydra tion, as deter- 
mined by actual analysis. 



ARSONO- AND ARSENOACETIC ACIDS 7 

2. If the thick paste is not allowed to stand over night, 
filtration is more cumbersome and it is extremely difficult to 
wash the precipitate free from arsenites. With this precaution, 
it is found that after five washings with 25<D-cc. portions of water, 
the final filtrate, as well as the desired barium salt, is practically 
free from iodine-reducing compounds. 

3. Stirring is required during the crystallization process, 
since otherwise the product tends to form a solid cake. The 
sodium salt is obtained without water of crystallization. 
Usually, it contains a trace of sulfate but this does not interfere 
with its subsequent use. The sulfate may be removed by 
recrystallization from water. 

3. Other Methods of Preparation 

Arsonoacetic acid was obtained by Ehrlich and Bertheim l 
by treating /?-aminophenylarsenoacetic acid with bromine. It 
has been prepared by the action of three molecular equivalents 
of sodium chloroacetate on two of sodium arsenite, followed by 
isolation as the calcium salt, 2 but it is found that these pro- 
portions are less satisfactory than the ones adopted. 3 Arseno- 
acetic acid has been prepared recently by Palmer. 3 

1 Ber. 43, 926 (1910). 

2 U. S. Pat. 1,445,685; Austrian Pat. 93,325; Swiss Pat. 97,977. 

3 J. Am. Chem. Soc. 45, 3023 (1923). 



IV 
a-BROMO-n-CAPROIC ACID 

CH8(CH 2 )4C0 2 H+Br2(PCl 3 ) -> CH 3 (CH.,) 3 CHBrCO 2 H+HBr 

Prepared by II. T. CLARKE and E. R. TAYLOR. 
Checked by C. S. MARVEL and R. L. SIIRINER. 

1. Procedure 

Two HUNDRED grams of freshly distilled dry w-caproic acid 
is placed in a i-l. flask with 300 g. of bromine which has been 
dried by washing once with 200 cc. of concentrated sulfuric 
acid (Note i). A j-cc. portion of phosphorus trichloride is 
cautiously added and the flask connected to a reflux condenser 
(Note 2), the top of which is connected with a trap and absorp- 
tion bottle containing water. The mixture is then heated in a 
water or oil bath to 65-70, at which temperature the reaction 
commences and hydrobromic acid is given off smoothly. After 
five to six hours, the bromine has all reacted (Note 3). Towards 
the end of the reaction, the temperature is allowed to rise to 
about 100. The contents of the flask are now distilled under 
diminished pressure (Note 4). The fraction boiling at 132- 
I40/i5 mm. is collected and amounts to 280-298 g. (81-80 
per cent of the theoretical amount). 

2, Notes 

1. The reagents must be dry or the yield will be lowered. 

2. A flask fitted with a ground -glass connection to the reflux 
condenser will assist in reducing the amount of tar. 

3. For larger runs, a longer time is required. A run of 2 kg. 
of caproic acid requires about fifteen hours. 

9 



10 ORGANIC SYNTHESES 

4. It is best to distil the first low-boiling fractions with a 
water pump, since a considerable amount of hydrogen bromide 
is evolved. In order to obtain a light-colored product, the dis- 
tillation should take place under as low pressure as possible. 
The a-bromo-ft-caproic acid boils at n6-i25/S mm. The 
product obtained is sufficiently pure for most purposes; upon 
redistillation, however, it comes over almost entirely between 
i28-i3i/io mm. 

3. Other Methods of Preparation 

a-Bromo-w-caproic acid has been prepared by heating 
n-caproic acid with bromine in a sealed tube to 140 l and with 
bromine and phosphorus; 2 also by the action of heat on 
a-bromobutylmalonic acid. 3 

*Z. Chem. 1868, 616; J. prakt. Chem. (2) 1, 7 (1870). 

2 Ber. 24, 2222 (1891); 33, 2381 (1900); Z. physiol. Chem. 86, 455 (1913). 

8 J. Am. Chem. Soc. 42, 319 (1920). 



V 
n-BUTYLMALONIC ESTER (ETHYL) 



Prepared by ROGER ADAMS and R. M. KAMM. 

Checked by F. C. WHITMORE and MILTON PUTERBAUGH. 

1. Procedure 

A 5-!. round-bottom flask, fitted with a rubber stopper 
holding a reflux condenser, a separatory funnel, and a mechani- 
cal stirrer, is clamped over a steam or water bath. In the flask 
is placed 2.5 1. of absolute alcohol (Note i) and then there is 
added gradually, through the condenser, 115 g. of clean sodium 
cut into pieces of suitable size. If the action becomes too 
violent, the mixture may be cooled by water poured over the 
outside of the flask. The sodium alcoholate solution is stirred, 
and cooled to about 50, after which 825 g. (780 cc.) of diethyl 
malonate (Note 2) is added slowly through the separatory 
funnel. To the clear solution is added gradually 685 g. (545 cc.) 
of w-butyl bromide (Note 3). The reaction commences almost 
immediately and considerable heat is generated. If the addi- 
tion is too rapid, the reaction may become violent enough to 
require cooling of the flask by pouring water over it. Up to 
this point, the time required is about two hours. 

The reaction mixture is refluxed until neutral to moist 
litmus; this requires about two hours. The flask is then con- 
nected with a condenser set for distillation. As much alcohol 
as possible is distilled off by means of the steam or water bath. 



12 ORGANIC SYNTHESES 

A period of about six hours is required for this distillation and 
about 2 1. of alcohol is recovered. 

The residue from which no more alcohol can be distilled is 
treated with about 2 1. of water and shaken thoroughly. The 
upper layer of ;z-butylmalonic ester is separated (Note 4) and 
distilled under diminished pressure from a 2- or a 3-!. Claisen 
flask. First a low-boiling portion is collected, consisting 
of alcohol, water, and butyl bromide; then a small inter- 
mediate fraction of unchanged malonic ester comes over; 
and finally w-butylmalonic ester boiling at i4o-i45/4 mm., 
I30-i35/ 20 nim., and 235-24o/76o mm . The first fractions 
amount to less than 100 cc., while the main fraction amounts to 
860-970 g. (80-90 per cent of the theoretical amount). 

2. Notes 

1. The quality of the absolute alcohol used has a very 
marked effect upon the yield. It is a wise procedure to reflux 
ordinary " absolute " alcohol with about one- twentieth of its 
weight of sodium and then to distil it directly into the flask in 
which it is to be used. 

A trial run with alcohol of 98.4 per cent purity gave only a 
66 per cent yield. 

2. The malonic ester used should be redistilled, preferably 
under diminished pressure, and a 2-degree fraction used in the 
preparation. Ordinary commercial malonic ester contains up 
to 15 per cent of low-boiling impurities. 

3. Redistilled w-butyl bromide boiling over a i -degree range 
should be used. 

4. It is not practical to filter off the sodium bromide either 
before or after the distillation of the alcohol, as the separation 
of the ester from the water layer is then very difficult. 

3. Other Methods of Preparation 

H-Butylmalonic ester has been prepared only by the action 
of n- butyl halides on sodium malonic ester. 1 

1 Ber. 28, 2622 (1895); J. Am. Chem. Soc. 42, 316 (1920). 



VI 

o-CHLOROMERCURIPHENOL 

C 6 H 5 OH+Hg(OCOCH3) 2 -> 



HOC 6 H 4 HgOCOCH 3 +NaCl -> CH 3 C0 2 Na+HOCoII 4 HgCl 

Prepared by F. C. WHITMORE and E R. HANSON. 
Checked by J. H. C'ONANT and R. M. GRANARA. 

1. Procedure 

Two liters of water is heated to boiling in a 3-!. flask. Mean- 
while 50 g. of phenol, in a 250-00. tall beaker provided with a 
small glass mechanical stirrer, is heated to 170 on an electric 
heater (Note i). The heat is then turned off and TOO g. of 
powdered mercuric acetate is added gradually (five to ten 
minutes) to the stirred phenol. After all of the mercuric ace- 
tate has dissolved in the phenol, the mercuration mixture is 
poured slowly into the hot water, the burner having previously 
been removed (Note 2). The beaker is rinsed out with some of 
the hot water. The mixture is boiled for five minutes and then 
filtered through filter paper in a large Buchner funnel which has 
been previously heated by blowing steam through it. The 
pink residue (Note 3) consists of a small amount of dimercurated 
phenol and some polymerization products. 

The filtrate is again brought to boiling in a clean flask and 
treated with a solution of 20 g. of sodium chloride in 200 cc. of 
boiling water. The precipitate formed is ^-chloromercuri- 
phenol together with some colored impurities (Note 4). The 
mixture is heated to boiling and filtered through a large pre- 
heated Buchner funnel. The filtrate on cooling deposits white 
feathery crystals of 0-chloromercuriphenol. The mixture is 

13 



14 ORGANIC SYNTHESES 

* 

allowed to stand at least twelve hours and then filtered. The 
crystals are air-dried. They should be colorless and should 
melt above 147 (m.p. of pure substance 152). If the product 
is pink or melts low it should be recrystallized from hot water. 
The average yield of fifteen experiments was 45 g. of ortho 
compound melting above 147, which corresponds to 44 per cent 
of the theoretical amount. 

2. Notes 

1. Mercuration at lower temperatures than that recom- 
mended gives a poorer yield of the ortho compound. 

2. If the heat is not removed from under the water before 
the mercuratecl phenol is added, the mixture is likely to froth 
over. 

3. Long heating of the mercuration mixture increases the 
amount of pink by-product. 

4. The yield of impure para compound obtained as a by- 
product varies from 10 to 30 g. 

5. A saturated solution of bromine in glycerol should be 
kept at hand as an antidote for phenol burns. If all undis- 
solved bromine is allowed to settle out before the solution is 
used, there is no danger of bromine burns. 

3. Other Methods of Preparation 

Phenol has been mercurated in water solution 1 and without 
the use of any solvent but the phenol itself. 2 

1 Ber. 35, 2855 (1902). 

2 J. Am. Chem. Soc. 43, 622 (1921). 



VII 
CREATININE 

NH=C(NH 2 )N(CH3)CH 2 CO2H - 

/NH CO 

NH=C( | +H 2 O 

\N(CH 3 ) CH 2 

Prepared by GRAHAM EDGAR and W S. HINEGARDNER. 
Checked by II. T. CLARKE and Ross PHILLIPS. 

1. Procedure 

A. Creatinine. A mixture of 900 g. of commercial creatine 
hydrate (Note i) with 550 cc. of concentrated hydrochloric 
acid (sp. gr. 1.19) and 150 cc. of water is warmed in a 3-!. flask 
on the steam bath for twenty-four hours. The hot solution is 
filtered and chilled to 0-5 in an ice bath, and to it is added 
1000 cc. of 28 per cent aqueous ammonia (sp. gr. 0.90). The 
flask is immersed in an ice-salt bath and the mixture is stirred 
vigorously until the temperature falls to o, when the crystal- 
line creatinine is filtered off, washed with ice-cold 28 per cent 
aqueous ammonia (Note 2) until the filtrate is free of chlorides, 
and finally with ice-cold methyl alcohol; the product (Note 3) 
is then dried to constant weight at 40-50. The yield (Note 4) 
is 545-555 g. (80-8 1 per cent of the theoretical amount). 

B. Creatinine Zinc Chloride. An intimate mixture of 400 g. 
of commercial creatine hydrate and 400 g. of fused zinc chloride 
is heated in a porcelain dish over a small flame. The mixture 
melts to a viscous liquid which soon solidifies. The flame is 
removed when the mixture can no longer be stirred. The mass, 
when cold, is broken up, and stirred with 500 cc. of cold water 
until the lumps are softened; the crude creatinine zinc chloride 
is filtered off with suction, by the use of a hardened filter paper, 

15 



16 ORGANIC SYNTHESES 

and washed with ice water to remove excess zinc chloride. The 
crude material is now dissolved in 6 1. of boiling 25 per cent 
aqueous acetic acid, filtered with the use of a little decolorizing 
carbon, and the solution allowed to stand for forty-eight hours. 
The crystals that have separated are filtered off, washed with 
ice water, and dried. Weight 220-230 g. The filtrate and 
washings are evaporated to 4.5 1. under reduced pressure in a 
12-1. flask; 6.5 1. of methyl alcohol is added and the mixture 
allowed to stand in a cool place for twenty-four hours. The 
crystals that separate are filtered off, washed with cold water 
and dried, and an additional 150-160 g. is thus obtained. The 
total yield is 370-380 g. (76-78 per cent of the theoretical 
amount) . 

C. Creatinine Picrate. A mixture of 300 g. of commercial 
creatine hydrate with 190 cc. of concentrated hydrochloric acid 
(sp. gr. 1.19) and 50 cc. of water is warmed in a glass or porce- 
lain dish on a steam bath for twenty-four hours. The resulting 
mass of creatinine hydrochloride crystals is dissolved in i 1. of 
water, boiled with a little decolorizing carbon, and filtered. 
The solution is then diluted to 4 1. with distilled water, and 
heated to boiling in a 12-!. flask under a reflux condenser. To 
the hot solution is added, with good stirring, a solution of 500 g. 
of technical picric acid (containing 10 per cent of water) in 
1250 cc. of warm methyl alcohol. Stirring is continued for one 
hour on the steam bath and the solution allowed to cool. The 
crystalline precipitate of creatinine picrate is filtered off, washed 
well with cold water, and dried. It forms long needles which 
melt at 220; the melting point (Note 5) is unchanged on recrys- 
tallization from hot water. The yield is 620-630 g. (89-90 per 
cent of the theoretical amount) . 

2. Notes 

i. As a rule, the commercial product, which contains one 
mol of water of crystallization, is entirely satisfactory; but if it 
is dark in color, it may be recrystallized from water with the 
use of decolorizing carbon. 



CREATININE 17 

2. Creatinine dissolves readily in pure water but is only 
slightly soluble in cold concentrated ammonia, while ammonium 
chloride is freely soluble. 

3. The creatinine so prepared is practically 100 per cent 
pure; its recrystallization, while not recommended, may be 
carried out by dissolving, as rapidly as possible, i part by weight 
in 5 parts of water previously warmed to 65, and then immedi- 
ately adding to the warm solution double its volume of acetone, 
chilling in ice, and filtering after a few hours. The product is 
finally washed with acetone and dried. About one-third is lost 
in the nitrate. 

4. The yield could be slightly increased by so modifying the 
conditions that the total volume of filtrate would be smaller, 
but this would involve an undue amount of trouble. 

5. Special attention was given to the melting point deter- 
mination, since two values, 205 and 212-213, have been 
recorded in the literature. 

3. Other Methods of Preparation 

Creatinine has been prepared generally from urine ] or 
muscle, 2 though its formation from creatine by the action of 
mineral acids has also been studied. 3 The conversion of crea- 
tine into creatinine has also been effected by heating in an 
autoclave * and by treatment with zinc chloride/ 5 The above 
technique has been developed rt since creatine has become avail- 
able in relatively large quantities as a by-product. 7 

1 Ann. 119, 39 (1861); 159, 279 (1871). 

2 Gazz. chim. ital. 17, 382 (1887). 

3 Ann. f>2, 298 (1847); J Am. Chem. Soc. 45, 2242 (1923). 

4 J. Biol. Chem. 8, 399 (1910). 

6 Jahresb. 1857, 544; J. Biol. Chem. 18, 183 (1914). 

6 J. Biol. Chem. 50, 3, 88 1 (1923). 

7 J. Ind. Eng. Chem. 14, 984 (1922). 



VIII 
CUPFERRON 

C G H5NHOH+C4H 9 ONO+NH3 - 



C H 5 N(NO)ONH4+C4H 9 OH 

Prepared by C S. MARVEL. 
Checked by OLIVER KAMM. 

1. Procedure 

THE moist phenylhydroxylamine obtained from 1000 g. of 
nitrobenzene, by the method described on page 57, is weighed 
and dissolved in 4.5 1. of ordinary ether (Note i). The ether- 
insoluble material (sodium chloride and water) is also weighed, 
the difference between the two weighings being a fairly accurate 
measure of the amount of phenylhydroxylamine in solution. 

The ether solution is filtered through a dry filter paper into a 
5-1. round-bottom flask which is fitted with an efficient mechani- 
cal stirrer and immersed in an ice-salt bath. When the tempera- 
ture of the solution has fallen to o (Note 2), a rapid stream of 
dry ammonia gas, from a cylinder of compressed gas, is passed 
into the solution. 

After about fifteen minutes, the theoretical amount of 
freshly distilled w-butyl nitrite (95 g. for every 100 g. of phenyl- 
hydroxylamine) is added slowly through a dropping funnel 
(Note 3). The addition of butyl nitrite usually requires about 
one hour (Note 4), during which time the stream of ammonia 
gas is continued in order that ammonia may always be in excess. 
If this precaution be not observed, a colored product will result. 
The temperature of the reaction mixture should be maintained 
below 10 and this may be done best by controlling the rate at 
which the butyl nitrite is added. An appreciable rise in tem- 

19 



20 ORGANIC SYNTHESES 

perature will cause the volatilization of considerable quantities 
of ether and of ammonia (Note 5). 

After the butyl nitrite has been added, the reaction mixture 
is stirred for about ten minutes longer in order to insure com- 
pletion of the reaction, after which the cupferron is filtered off 
and washed several times with small portions of fresh ether. 
The product is spread on sheets of paper until all traces of ether 
have been lost, and is then stored in bottles where it is exposed 
to the vapors of ammonium carbonate. This may be done by 
protecting each cork with a double sheet of filter paper and 
placing a lump of ammonium carbonate between the cork and 
the filter paper. 

The yield of cupferron from a given weight of phenylhydroxyl- 
amine averages 85-90 per cent of the theoretical amount. 

2. Notes 

1. The solvent ether may be replaced by benzene, but this 
modification offers no advantages for the preparation of cup- 
ferron on a laboratory scale. 

2. The temperature must be kept low. If it is not, the 
material is generally colored brown and the reaction does not 
run smoothly. Probably the most important factor in securing 
successful results is always to have an excess of ammonia present. 

3. The butyl nitrite is freshly distilled as a general pre- 
caution, because a product which has stood for some time is 
often partially decomposed. 

4. In the preparation of cupferron, it has been recommended 
that the butyl nitrite be added all at one time. This pro- 
cedure is satisfactory only when the amount of phenylhydrox- 
ylamine used is less than 200 g.; otherwise the reaction becomes 
extremely vigorous and an excessive proportion of ether is lost. 
The directions given above, on the other hand, are adaptable 
for the preparation of large quantities of cupferron. For the 
rapid preparation of small quantities of material, the butyl 
nitrite may be added all at one time, provided sufficient excess of 
ammonia is present. 



CUPFERRON 21 

5. It is found that 75 per cent of the ether and 95 per cent of 
the butyl alcohol used may be recovered, and that one man, work- 
ing six to seven hours, is able to prepare 800 g. of cupferron. 
The recovered ether may be used over again, provided the fol- 
lowing procedure is followed: The phenylhydroxylamine is dis- 
solved in a little fresh ether, the solution cooled and treated 
with ammonia, then the recovered ether added. This pre- 
caution is necessary owing to the presence of some butyl nitrite 
in the recovered ether. 

3. Other Methods of Preparation 

Nitroso-^phenylhydroxylamine, of which cupferron is the 
ammonium salt, has been made by the action of sodium nitrite 
and hydrochloric acid on /3-phenylhydroxylamine, 1 of hydrogen 
peroxide on normal phenykliazotates, 2 of sodium alcoholate and 
hydroxylamine on nitrobenzene, 3 of nitric oxide on phenyl 
magnesium bromide, 4 and by the action of permonosulfuric acid 
on aniline in the presence of amyl nitrite. 5 

Cupferron has usually been prepared from a mixture of alkyl 
nitrite and /3-phcnylhydroxylamine in the presence of ammonia 
in ether or benzene solution/ 1 but it has also been made by the 
zinc dust reduction of nitrobenzene in the presence of amyl 
nitrite and ammonium hydroxide solution. 7 

1 Ber 27, 1435, 1554 (1894); 52B, 1839 (1919); J. Am. Chem. Soc.41, 280 (igig). 
2 Ber. 42, 3575 (1909). 

3 Ber. 29, 1885 (1896). 

4 Ann. 329, 191 (1903). 

5 D. R. P. 227,659; Frdl. 10, 126 (1910). 

6 Chem. Z. 35, 913 (1911); J. Ind. Eng. Chem. 3, 629 (1911); 12, 799 (1920); 
J. Am. Chem. Soc. 41, 280 (igig). 

7 D. R. P. 227,659; Frdl. 10, 126 (1910). 



IX 

DI-p-TOLYLETHANE (unsym.) 
2C 6 H 5 CH 3 +CH=CH(HgS04) - 



Prepared by J. S. REJCHERT and J. A. NIEUWLAND. 
Checked by OLIVER KAMM. 

1. Procedure 

A 2-1. flask, containing 700 cc. of toluene, 70 cc. of concen- 
trated sulfuric acid, and 7 g. of mercuric sulfate, is fitted with a 
stirrer, a thermometer reaching into the liquid, and an inlet 
tube connected with a gasometer containing acetylene, as 
shown in Fig. i (Note i). The flask and its contents are 
tared and cooled to 10 before the absorption of acetylene is 
begun. The gas from the tank, A , is washed free from acetone 
by being passed first through water in the gasometer, B, and 
then through the concentrated sulfuric acid wash bottle, C. 

The acetylene is absorbed rapidly, with the evolution of 
considerable heat. The temperature of the reaction mixture is 
maintained at 10-15 by immersing the flask in a freezing mix- 
ture. When at intervals the reaction slows down, it becomes 
necessary to sweep the system free from air which accumulates 
in the flask. The absorption is continued until about 60 g. of 
acetylene has been absorbed, which requires a period of about 
two hours (Note 2). During the absorption, the mixture turns 
first a reddish brown, then a dark brown, and finally almost 
black. 

The reaction mixture is freed from the acid by washing once 
with pure water and then with sodium carbonate solution, to 
which some sodium chloride is added to aid the separation of 

23 



24 



ORGANIC SYNTHESES 



the hydrocarbon layer. If emulsification takes place, the addi- 
tion of ether will remedy the difficulty. 

The toluene layer is transferred to a i-l. flask, without drying, 
and the unchanged toluene distilled off; the ditolylethane is 
then collected over a range of 295-310. There is practically 
no intermediate fraction, but a tarry residue of about 75 g. 
remains in the flask. Upon redistillation, the ditolylethane is 




FIG. i. 

collected at 295-300. The yield is 290-310 g. (60-64 per cent 
of the theoretical amount) (Note 3). 

2. Notes 

i. The acetylene is absorbed with unexpected rapidity so 
that it is unnecessary to deliver the gas beneath the surface of 
the liquid. In an ordinary reaction involving a gas it would 
be advisable to use a special stirrer of the type illustrated in 
Org. Syn. 3, p. 29, and to deliver the gas beneath the dis- 
tributing tube of the stirrer. 



DI-/-TOLYLETHANE (unsym.) 25 

2. It is scarcely necessary to remove the flask for weighing 
until near the end of the experiment, since the volume of acetylene 
is known and practically complete absorption takes place. If 
a tank of compressed gas is not available, the acetylene may be 
prepared from calcium carbide by the usual laboratory methods. 1 

3. Subsequent redistillation yields a product boiling prac- 
tically over a 2-degree range. The best product was obtained 
by a final fractionation under diminished pressure, when the 
boiling point was found to be 144-1 45 /8 mm. 

4. Xylene, mesitylene, ethylbenzene, and benzene condense 
with acetylene in a manner similar to that described above for 
toluene, although the yields are usually lower. 2 

3. Other Methods of Preparation 

Ditolylethane has been obtained also from the reaction 
between paraldehyde and toluene in the presence of sulfuric 
acid, 3 from the reaction between ethylidene chloride and toluene 
in the presence of aluminium chloride, 4 and by heating a-ditolyl- 
propionic acid in the presence of lime. 5 

l Ct. C. A. 3, 2887 (1909). 

2 J. Am. Chem. Soc. 45, 3090 (1933) 

3 Bcr 7, 1193 (1874). 

4 Ann. 235, 313 (1886). 

6 Her. 16, 1476 (1882) 



X 
ETHYL OXOMALONATE 

2 H 5 )2 + 2N2O3 -> CO(CO 2 C 2 H 5 ) 2 +H 2 O+4NO 

Prepared by A. W. Dox. 

Checked by C. S. MARVEL and R. L. SHRINER. 

1. Procedure 

INTO a 500-00. Erlenmeyer flask containing 200 g. of ethyl 
malonate, and cooled to o by surrounding with cracked ice and 
salt, a rapid current of nitrous anhydride is passed. The gas is 
generated by dropping concentrated nitric acid through a separa- 
tory funnel upon dry arsenious oxide contained in a 500-00. 
Florence flask placed upon a tripod and wire gauze. The arseni- 
ous oxide should be in lumps about the size of a pea. An empty 
flask is inserted between the generator and the absorption flask 
and the gas dried by passage through a calcium chloride tube 
(Note i). As the evolution of gas slows down, gentle heat may 
be applied with a burner. The ethyl malonate becomes dark 
green in color. There should be an increase in weight of about 
200 g. in two to three hours. 

The liquid is left in the freezing mixture for several hours, 
then gradually allowed to come to room temperature (Note 2). 
Red gases are slowly evolved. After standing for two days or 
more at room temperature, the liquid is transferred to a distilling 
flask provided with a capillary air intake, and the delivery tube 
connected with a water-cooled condenser and receiver. The 
distillation is performed under diminished pressure, by the use 
of a water pump. Considerable nitric oxide is evolved before 
the pressure drops to about 70 mm. (Note 3). 

The first fraction consists mainly of water, a little ethyl 
acetate, and some ethyl oxomalonate which recombines with the 
water to form ethyl mesoxalate. When the pressure has dropped 
to 45 mm. and the temperature has risen to 110, the receiver is 

27 



28 ORGANIC SYNTHESES 

changed (Note 4). The main product, ethyl oxomalonate, now 
distils at no-i35/45~5o mm. If the oxidation has been com- 
plete, very little residue is left (Note 5). Redistillation gives a 
golden-yellow liquid boiling between io3-io8/i5 mm. The 
yield is 160-165 g. (74-76 per cent of the theoretical amount). 

2. Notes 

1. The yield of ethyl oxomalonate is decreased if the nitrous 
anhydride is not dried. 

2. If the temperature is raised too rapidly, the liberation of 
gases causes the mixture to boil too vigorously. 

3. A motor pump is not recommended because the nitric 
oxide is apt to cause corrosion. If too high a vacuum is used at 
first, a residue of ethyl iso-nitrosomalonate may remain. 

4. The remainder of the distillation must be conducted with 
extreme care. As soon as the ethyl oxomalonate has partly 
distilled over and the temperature has risen somewhat, the 
remaining iso-nitroso compound begins to decompose and some- 
times liberates gases so rapidly that the thermometer and capil- 
lary tube may be blown out of the flask. If the manometer is 
watched closely, and at the first sign of liberation of gas, as 
evinced by a sudden increase in pressure, a wet towel is placed 
around the flask, the reaction can be slowed down. 

5. In case any considerable amount of residue remains above 
135 at 45 mm., it is heated at ordinary pressure to a higher 
temperature until no more nitric oxide is given off, then distilled 
as before. 

3. Other Methods of Preparation 

Ethyl oxomalonate is obtained from a variety of interme- 
diates 1 but the only method which appears of practical value 
consists in the oxidation of ethyl malonate by means of oxides 
of nitrogen. This reaction, carried out in two steps by Bouveault 
and Wahl, 2 was studied by Schmidt 3 and subsequently con- 
siderably improved by Curtiss 4 and also by Meyer. 5 

1 Beilstein, 3, 769-770 (Fourth Edition). 2 Compt. rend. 137, 196 (1903). 

8 Compt. rend. 140, 1400 (1905). 4 Am. Chem. J. 33, 603 (1905); 35, 477 (1906). 

6 Bull. soc. chim. (4) 9, 423 (1911); C. A. 5, 3229 (1911). 



XI 
ETHYL PROPANE-M,2,3-TETRACARBOXYLATE 



(C 2 H 5 ONa) 

Prepared by H. T. CLARKE and T. F. MURRAY. 
Checked by C. S. MARVEL and M. M. BRUBAKER. 

1. Procedure 

IN a 5-1. flask, fitted with a stirrer, reflux condenser, and 
dropping funnel, is placed 1000 g. of absolute ethyl alcohol; 
92 g. of sodium, cut into strips, is then added through the con- 
denser at such a rate that the alcohol does not boil too vigor- 
ously. When all the sodium is in solution, the flask is cooled 
and 800 g. of ethyl malonate added through the condenser, with 
stirring. The mixture is warmed gently on the steam bath and 
700 g. of ethyl fumarate (Note i) added from the dropping 
funnel. During this addition the solution is kept boiling gently, 
heat being applied if necessary (Note 2) . The mixture is boiled 
for one hour after the ethyl fumarate has been added. It is 
then cooled and 250 g. of glacial acetic acid is added. 

Most of the alcohol is distilled off under slightly reduced 
pressure on the steam bath and the residue is poured into suffi- 
cient distilled water to dissolve all the solid. The water layer 
is separated and extracted four times with carbon tetrachloride, 
which is added to the ester layer. The ester-carbon tetrachlo- 
ride mixture is washed twice with water and the water washings 
extracted once with carbon tetrachloride. The carbon tetra- 
chloride is distilled off under atmospheric pressure through a 
column, the moisture being carried over simultaneously. 

29 



30 ORGANIC SYNTHESES 

The residue is then distilled under reduced pressure, when 
the ethyl propane- 1,1, 2, 3-tetracarboxylate comes over at 
i82-i84/8 mm. The yield is 1261-1273 g. (95-96 per cent of 
the theoretical amount). 

2. Notes 

1. The ethyl malonate and ethyl fumarate should be redis- 
tilled under reduced pressure, and the material boiling over a 
2-degree range should be collected. 

2. Heat is developed during the reaction, and the mixture 
may be kept boiling by adding the ethyl fumarate at a suitable 
rate. 

3. Other Methods of Preparation 

Now that fumaric and maleic acid are available commercially, 
the most convenient method of preparing the above ester con- 
sists in condensing ethyl malonate with ethyl fumarate 1 or ethyl 
maleate. 2 It has also been prepared by condensing malonic 
ester with ethyl chlorosuccinate 3 and with ethyl ethoxysucci- 
nate. 4 

J Ber. 24, 2889 (1891), J. prakt. Chem. (2) 45, 56 (1892); J. Chem. Soc. 73, 
1007 (1898); Ann 341, 102 (1905) 
2 J. prakt. Chem (2) 45, 56 (1892). 
Ber 23,375Q(i89o). 
4 Chem. Zentr. 1903 (II), 943; Ann. 341, 104 (1905). 



XII 

GLYCINE 
CH 2 =NCH 2 



CH 2 O+HBr NH 2 CH 2 C0 2 H+NH 4 Br 

HBr NH 2 CH 2 CO 2 H + C 5 H 5 N -> 

NH 2 CH 2 C0 2 H + C 5 H 5 N - HBr 

Prepared by H T CLARKE and E. R. TAYLOR. 
Checked by ROGER ADAMS and W. F. TULEY. 

1. Procedure 

IN a 5-1. flask fitted with a downward condenser, are placed 
340 g. of methylene aminoacetonitrile (p. 47) and 2500 g. of 
48 per cent hydrobromic acid (Note i). The mixture is heated 
on the steam bath for three hours (Note 2). The pressure in 
the apparatus is then reduced and dilute acid and formaldehyde 
are distilled into a water-cooled receiver until the separation of 
ammonium bromide from the reaction mixture causes bumping. 
This occurs when approximately half of the liquid has been dis- 
tilled over. The ammonium bromide is filtered from the hot 
liquid and washed with a small amount of cold water; the 
filtrates are returned to the flask and distillation continued as 
nearly as possible to dryness (Note 3). The residue is dissolved 
in 2 1. of cold methyl alcohol and filtered; to the filtrate is added 
350 cc. of pyridine, with vigorous shaking (Note 4). 

The mixture is allowed to stand over night and the precipi- 
tated glycine filtered off and washed with methyl alcohol 
(Note 5) until the washings are free from bromides. The prod- 
uct is dissolved in 300 cc. of boiling distilled water and the solu- 
tion filtered with the use of a little decolorizing carbon; the 
filtrate is allowed to cool to 40-50, when 1500 cc. of methyl 
alcohol is added with hand stirring. If the product is colored, 
the procedure, just described, of dissolving in water and repre- 
cipitating with methyl alcohol is repeated. The glycine that 

31 



32 ^ ORGANIC SYNTHESES 

separates is filtered off when the mixture is cold and washed with 
methyl alcohol until a sample (Note 6) is found to be free from 
ammonia on testing with Nessler solution (Note 7). If a second 
precipitation is made, the glycine is practically free from ammo- 
nium salts and washing with methyl alcohol is unnecessary. 
Not more than i 1. of methyl alcohol should be necessary for 
this purpose; if positive tests continue to be obtained, an 
ammonia-free product may be secured by treating the aqueous 
solution for a short time with a water-softening zeolite, filtering 
and crystallizing or precipitating with alcohol. 

The yield is 115-140 g. (31-37 per cent of the theoretical 
amount) of a colorless product which melts with decomposition 
at 225-230 (Note 8). 

The distillate from the reaction mixture may be redistilled 
under atmospheric pressure with the use of a column; the 
fraction boiling at 125-126 may be collected, when one-third 
to one-half the amount of hydrobromic acid originally taken can 
be recovered. The foreruns contain formaldehyde. 

2. Notes 

1. If preferred, 3000 g. of 40 per cent acid may be taken. 
Hydrobromic acid is employed in preference to other mineral 
acids on account of the high solubility of ammonium bromide in 
methyl alcohol. 

2. Hydrolysis takes place readily, with a slight evolution of 
heat, so that actual boiling over a free flame is unnecessary. 

3. The residue consists of a syrup (largely glycine hydro- 
bromide) mixed with crystals of ammonium bromide. It has a 
strong odor of formaldehyde. 

4. A technical grade of pyridine may be employed if this is 
colorless and distils not lower than 100 nor higher than 140. 

5. Ammonium bromide dissolves in about eight times its 
weight of methyl alcohol. It is much less soluble in absolute 
ethyl alcohol, requiring about 30 parts of that solvent. 

6. The sample should be taken from the lower part of the 
cake on the funnel by means of a glass tube, since the upper 
layers become free of impurities first. 



GLYCINE 33 

7. The sample of glycine must be dry before testing, as 
traces of impurities generally present in the methyl alcohol give 
a precipitate with Nessler solution. To carry out the test, 
0.1-0.2 g. of dry product is dissolved in 3 to 5 cc. of distilled 
water containing a few drops of sodium hydroxide solution, and 
i cc. of Nessler solution is added. 

8. A further small quantity of impure glycine can be iso- 
lated by concentrating the filtrates obtained on recrystalliza- 
tion. The liquors from the first precipitation, containing 
ammonium bromide, pyridine hydrobromide, excess pyridine, 
and alcohol-soluble by-products, may be treated as follows: 
The mixture is first acidified with mineral acid and the methyl 
alcohol recovered by distillation with a column. The residue 
is rendered strongly alkaline and the bulk of the ammonia 
removed by boiling under a reflux condenser; wet pyridine can 
be recovered by downward distillation and treatment of the dis- 
tillate with solid sodium hydroxide. 

3. Other Methods of Preparation 

Glycine hydrochloride has been prepared by the action of 
hydrochloric acid upon hippuric acid, 1 upon aminoaceto- 
nitrile, 2 upon methylene aminoacetonitrile, 3 and upon ethyl 
phthaliminoacetate; 4 its conversion into free glycine by methods 
involving silver or lead oxides is apt to be troublesome. The 
classical method of preparing glycine by the interaction of 
chloroacetic acid and ammonia 5 is unsatisfactory, owing to the 
laborious process of isolation through the copper salt, which, 
moreover, rarely gives a product entirely free of ammonia. 
The hydrolysis of methylene aminoacetonitrile by successive 
treatments with barium hydroxide and sulfuric acid 6 furnishes 
a more satisfactory method, but the final product is seldom 
entirely pure, partly owing to the difficulty in obtaining pure 
barium hydroxide. The same objection applies to the hydrolysis 
of aminoacetonitrile by means of barium hydroxide. 7 

1 J prakt. Chem. (2) 37, 157 (1888). 6 Ann. 266, 205 (1891). 

2 Ann. 278, 236 (1894). 6 Biochem. J. 16, 702 (1922). 
Ber. 27, 60 (1894). 7 Ann. 278, 237 (1894). 
Ber. 22, 428 (1889). 



XIII 
HYDROXYHYDRO QUINONE TRIACETATE 

O=C G H 4 =0+2(CH a CO)2O-> OCOCH ;i 

1-OCOCH 3 

+ CH 3 COOH 
OCOCHs 

Prepared by K B. VLIET. 

Checked by ROGL.R ADAMS and H. O. CALVERY. 

1. Procedure 

TWELVE grams of concentrated sulfuric acid is added to 
1 80 g. of acetic anhydride in a 6oo-cc. beaker, after which 60 g. 
of benzoquinone (Note i) is added gradually in small portions 
with constant mechanical stirring. The temperature rises and 
should be held at 40-50 during the addition of the quinone. 
A temperature higher than 50 leads to decomposition of the 
product while a temperature lower than 40 causes a much 
slower reaction. Good temperature control can be obtained by 
using care in adding the quinone and by the use of a cooling 
bath and efficient stirring. The reaction goes smoothly and 
does not evolve an excessive amount of heat. 

After all the quinone has been added, the solution is allowed 
to stand. It should be watched closely at first to see that the 
temperature does not rise above 50, but at the same time it is 
well not to cool it below 40. When the mixture starts to cool 
of its own accord, a precipitate begins to form. As soon as the 
mixture has cooled to about 25 (Note 2), it is poured into 
750 cc. of cold water, whereupon a white precipitate separates. 
This is cooled to about 10 and filtered off with suction. The 

35 



36 ORGANIC SYNTHESES 

product is recrystallized from 250 cc. of 95 per cent ethyl aclohol 
and dried. The drying is best done in a vacuum desiccator, 
through which a very small stream of air is allowed to sweep. 
Calcium chloride is the best drying agent. 

The product is practically white and rather granular; it 
melts at 96-97. The yield is 120-123 g. (85-87 per cent of the 
theoretical amount). The product is fairly reactive and tends 
to decompose upon standing (Note 3), especially if care be not 
used in drying and handling. If it is to be used as a starting 
material for other syntheses, it is advisable to use it as soon as 
possible. 

2. Notes 

1. The quality of the product depends to a large extent upon 
the purity of the benzoquinone; if the latter is dark, it is advis- 
able to crystallize it from benzene before using it. (See Org. 
Syn. 2, 86.) 

2. It is quite desirable to have the reaction mixture cooled 
to about 25 before it is added to the water. If it is warm when 
added to the water, an oil will separate which solidifies slowly 
in the form of lumps. 

3. The hydroxyhydroquinone triacetate keeps quite satis- 
factorily in an atmosphere of carbon dioxide. 

3. Other Methods of Preparation 

The method described above is essentially the same as that 
of Thiele, 1 which has been patented by F. Bayer and Company. 2 
Hydroxyhydroquinone triacetate has also been obtained by 
acetylating hydroxyhydroquinone formed by the alkali fusion 
of hydroquinone. 3 

1 Ber. 31, 1247 (1898); Gazz. chim. ital. 40 (2) 349 (1910). 

2 D. R. P. 101,607 and 107,508; Frdl. 5, 155-6 (1898;. 

3 Monatsh. 5, 590 (1884). 



XIV 
o-IODOPHENOL 

2HOC 6 H 4 HgCl+2l 2 - Hgl2+HgCl2+2lC6H 4 OH 

Prepared by F C. WHITMORE and E. R. HANSON. 
Checked by J. B. CONANT and R. M. GRANARA. 

1. Procedure 

A 2-1. round-bottom short-neck flask is equipped with a 
glass mechanical stirrer. A suspension of 165 g. of 0-chloro- 
mercuriphenol (p. 13) (m.p. 147 or higher) in 500 cc. of chloro- 
form is placed in the flask and treated with 127 g. of iodine, the 
stirring being continued until a small sample on nitration shows 
no unreacted iodine. This requires from one to two hours. 
The solid inorganic mercury compounds are removed by suction 
filtration. The filtrate is distilled from a i-l. distilling flask on 
the water bath to remove most of the chloroform, which is 
saved for later runs (Note i). The residual liquid is shaken 
vigorously with a solution of 5 g. of potassium iodide in 10 cc. 
of water, to remove dissolved mercuric iodide. The heavier 
layer, which still possesses a reddish color, is transferred without 
drying to a 2oo-cc. Claisen flask and distilled under diminished 
pressure. At first a small amount of chloroform and water distils 
over, after which the higher-boiling material is collected in a 
separate receiver. Small amounts of inorganic mercury com- 
pounds remain in the flask (Note 2). 

The 0-iodophenol solidifies upon cooling. The yield of 
material melting at 32-34 is 70 g. (63 per cent of the theoretical 
amount). The product obtained in this way is slightly yellow. 
If a purer product is desired, it may be redistilled in vacuo. 

37 



38 - ORGANIC SYNTHESES 

Most of the crude material will distil over a 5-degree range 
(b.p. i3o/i8 mm. and i&6/i6o mm., m.p. 43). 

2. Notes 

1. About 460 cc. of chloroform can be recovered, the time 
required being one hour. 

2. The first distillation of the iodophenol should be carried 
out under a good vacuum, 40 mm. or lower. The redistillation 
may be conducted at a higher pressure if desired. 

3. Since the iodophenol has a most persistent odor, care 
should be exercised in working with it. A solution of bromine 
in glycerol may be used as an antidote for burns from the iodo- 
phenol (p. 14). 

3. Other Methods of Preparation 

0-Todophenol has been made by diazotization from 0-amino- 
phenol l and from 0-iodoaniline. 2 It has been obtained by 
heating 0-iodosalicylic acid. 3 Mixed with its para isomer and 
diiodophenol, it has been made by treating a dilute phenol 
solution with iodine and iodic acid, 4 and it has also been obtained 
from an alkaline solution of phenol and iodine in the presence of 
mercuric oxide, 5 and from dry sodium phenol ate and iodine in 
carbon disulfide. 6 

1 Ber. 8, 820 (1875); Ann. 241, 68 (1887). 

2 Chem. Zentr. 1910 (II;, 304. 

3 Ann. 120,315 (1861). 

4 Z. Chem. 1866, 662, 1868, 322. 
6 Ber. 2, 523(1869); 6,1251 (1873). 
8 Ber. 16, 1897 (1883), 20, 3363 (1887). 



XV 
KETENE 

CH 3 COCH 3 -> CH,i= 

1. Procedure 



Prepared by C. D. KURD. 
Checked by OLIVER KAMM. 



A. Preparation of ketcnc. The arrangement of the appara- 
tus is shown in Fig. 2 (Note i). The graduated separatory 
funnel, shown in the diagram, rilled with 125 cc. of commercial 
acetone, leads into a 5oo-cc. round-bottom flask which, in turn, 
is connected by gas-tight joints (Note 2) to a glass combustion 
tube filled with broken porcelain, a spiral or bulb condenser, a 
two-way stopcock, and a reaction flask. In the reaction flask 
is placed the material with which the ketene is to react (Note 3) . 
A second reaction flask may be placed in series, if desired, to 
ascertain if any ketene escaped reaction in the first flask. 

Prior to either of these steps, fourteen of the twenty burners 
of the combustion furnace are lighted (Note 4) and tiles are 
placed over the lighted burners, which finally must be adjusted 
to yield a maximum temperature. The first two and last four 
burners are unused. 

When the furnace is fully heated, boiling water is placed 
beneath the round-bottom flask and cold water passed through 
the condenser. Acetone is now dropped in at the rate of 3-4 cc. 
per minute. About half the acetone should be recovered as 
distillate in cylinder B (Note 5) . Ketene, admixed with methane, 
carbon monoxide, and ethylene, passes into the reaction flasks 
(Note 6) in 25-29 per cent yields. The flow may be interrupted 
at will by checking the acetone flow. 

39 



40 



ORGANIC SYNTHESES 



B. Preparation of acetanilide. Since ketene is a highly 
reactive gas, it is usually prepared for immediate consumption 
instead of being isolated as such. It reacts with various groups 
which contain hydrogen, such as hydroxyl, amino, mercaptan, 
hydroxylamino, etc., forming acetyl derivatives. 

Twenty-five grams of aniline is placed in the reaction flask, 
D, and 50 cc. of dry ether added as solvent (Note 7). A second 
reaction flask is connected at C, in which is placed 5 g. of aniline, 




5 




FIG. 2. 



dissolved in 20 cc. of ether. This prevents the escape of ketene 
vapor at the beginning and at the close of the operation (Note 5). 
In all, 85 cc. of acetone is passed through the apparatus, 39 cc. 
of which is recovered as distillate. Therefore, 44 cc. (or 35 g.) 
of acetone is decomposed. The duration of the run is about 
thirty minutes. Twenty-one grams of acetanilide, which cor- 
responds to a yield of 25.8 per cent, based upon the amount of 
acetone decomposed, is isolated from the reaction mixture. 

2. Notes 

i. The apparatus. A graduated dropping funnel and a 
graduated cylinder for the distillate are chosen because of con- 
venience in determining the volume of decomposed acetone. 



KETENE 41 

The bulb (or spiral) condenser is chosen because of its effi- 
ciency. With an ordinary condenser, it is necessary to insert 
two U-tubes, cooled by ice, between the condenser and the 
reaction flask, to remove all the acetone from the ketene. In 
many reactions, however, this admixed acetone will do no harm. 
This part of the apparatus is designed to eliminate the loss of 
ketene by solvent action, prior to its entry into the reaction 
flask. 

A wide-mouth delivery tube in the reaction flask is essential 
to prevent clogging, when a solid product is formed. Automatic 
stirring in the reaction flask may be used to advantage in certain 
instances. There is constant agitation, of course, as the gaseous 
decomposition products bubble through. 

Either Scotland glass or Pyrex is satisfactory for the com- 
bustion tube. An estimate of the temperature is 650 (Note 4). 
The life of the tube is lengthened if it rests upon a layer of thin 
asbestos paper. The tube is filled with pieces of broken porce- 
lain, to serve as a " heat reservoir "; there is no catalytic effect. 
The porcelain blackens during the reaction. 

2. Care in assembly. Since this is a gaseous reaction, it is 
essential that the apparatus be free from leaks; thus, corks are 
eliminated wherever possible. The ends of the combustion tube 
and the top of the condenser are drawn to the diameter of the 
connecting tubes and joined by a piece of thick-walled rubber 
tubing. Care should be taken to have the ends of the glass 
tubes come into contact. The rubber tube situated between 
the furnace and condenser is protected by the asbestos screen, 
but a further essential precaution is taken, namely, that this 
end of the combustion tube extend a considerable distance from 
the furnace. 

The stoppers in the reaction flask and at the top of the drop- 
ping funnel are of rubber; the other two are well-selected corks, 
bored perfectly and painted both inside and out with water- 
glass, one day previous to being used. 

3. The apparatus may be calibrated by allowing the ketene 
to react with sN alkali and titrating the excess alkali with acid. 

4. With an electric combustion furnace, wherein a tempera- 



42 ORGANIC SYNTHESES 

ture of 695-705 is maintained, consistent yields of 35-40 per 
cent ketene are produced. The best rate of flow in such a case 
is 4-6 cc. per minute, with recovery of 60-80 per cent of the 
original acetone as distillate. Although yields of ketene rang- 
ing above 45 per cent have been obtained frequently with this 
apparatus, they could not be duplicated consistently. 

5. The thermal decomposition of ketene into carbon mon- 
oxide and ethylene is prevented, as far as possible, by the rapid 
removal of ketene from the hot tube, which is accomplished by 
the undecomposed acetone vapor. About half the acetone 
originally used should be collected unchanged as distillate by 
the vertical condenser. The yield of ketene will fall consider- 
ably if less distillate is formed. 

6. Ketene gas is very irritant when breathed, and hence 
proper cautions should be taken to avoid inhalation. 

7. An ice bath surrounding the reaction flask is usually 
employed, not only to prevent the vaporization of the solvent, 
but also to promote a greater solubility of ketene. 

3. Other Methods of Preparation 

In addition to the above method, based upon the work of 
Schmidlin and Bergman 1 as modified by Hurd and Cochran, 2 
ketene has been prepared by the pyrogenic decomposition of 
acetic anhydride, 3 of ethyl acetate, and of triacetin. 4 In the 
last instance, acrolein and acetic acid are formed simultaneously, 

Ketene has also been formed by the action of zinc upon an 
ethereal solution of bromoacetyl bromide/ 3 Carbon monoxide 
and diazomethane, diluted with ether, when passed through a 
quartz tube at 400-500, yield ketene and nitrogen. 6 

iBer. 43, 2821 (1910). 

2 J. Am. Chem. Soc. 45, 515 (1923). 

3 J. Chem. Soc. 91, 1938 (1907); 97, 1968 (1910). 
Ber. 47, 2393 (1914). 

6 Ber. 41,594(1908). 
6 Ber. 45, 508 (1912). 



XVI 
0-METHYL ANTHRAQUINONE 

C0 2 H 



(H 2 S0 4 ) 
/\ / 

CO' 

/ \/ \y x/v"o 

H 2 




Prepared by L. F. Ficser. 

Checked by ROGER ADAMS and R. L. SIIRINER. 

1. Procedure 

THE />-toluyl-0-benzoic acid which is obtained from 100 g. 
of phthalic anhydride (p. 73), and which should weigh 157 g., 
is mixed with 1400 g. of fuming sulfuric acid (20 per cent anhy- 
dride) (Note i) in a 2-1. flask protected by a calcium chloride 
tube; and the mixture is heated on the steam bath for two 
hours with occasional shaking (Note 2). The clear, deep red 
solution is poured when cold upon cracked ice in a 4-!. beaker. 
The methyl anthraquinone separates and is digested for twenty 
minutes by passing in steam, after which it is filtered by suction. 
A flannel cloth is used in the filter, or a filtros plate may be 
cemented into a Buchner funnel with water-glass. The pre- 
cipitate is washed well with hot water, after which it is returned 
to the beaker and digested as before with hot water to which 
is added a slight excess of ammonia, beyond that required to 
neutralize any acid present. 

The product is filtered and dried to constant weight. The 
filtrate will be clear and will give no precipitate with hydro- 
chloric acid if the conditions of condensation have been correct. 

The 0-methyl anthraquinone is pale tan in color and weighs 
from 118 to 130 g. (86-95 per cent of the theoretical amount, 
based upon the weight of acid taken). It is practically pure, 
melting at 173. Upon crystallization from alcohol in the 
presence of bone-black, it forms long, silken, almost colorless 
needles, melting constantly at 173.5 (176 cor.). 

43 



44 ' ORGANIC SYNTHESES 

2. Notes 

1. Some investigators have used concentrated instead of 
fuming sulfuric acid for the condensation, but the yield is usually 
low and the product is always colored bright yellow by some 
impurity which cannot be removed by crystallization. 

2. The time allowed for condensation may be shortened to 
one-half, without affecting the yield, by maintaining the tem- 
perature at 125-130 for this length of time. 

3. Other Methods of Preparation 

/3-Methyl anthraquinone has been obtained by the oxida- 
tion of /3-methyl anthracene by several investigators; l and 
material of the same origin, obtained by the benzene-extraction 
of crude commercial anthraquinone, 2 has been fully described. 
As regards the synthesis from phthalic anhydride and toluene, 
both the preparation and properties of />-toluyl-o-benzoic acid 3 
and the complete synthesis 4 have been the subject of several 
papers. This acid has also been prepared from 0-carbomethoxy 
benzoyl chloride and toluene. 5 The phthalic anhydride syn- 
thesis of anthraquinone derivatives in general has received con- 
siderable attention. An account of this work, together with 
extensive references, is given by Barnett. 6 

The following unimportant preparative methods may be 
mentioned: the production of /3-methyl anthraquinone by the 
reduction of 2-bromo-3 -methyl anthraquinone; 7 the oxidation 
of /3-methyl anthracene-7-carboxylic acid; 8 and the reduction 
of 2 -methyl anthraquinonyl-i-diazonium sulfate. 9 

1 Ber. 8, 675 (1875); J. prakt. Chem. [2] 79, 560 (1909); [2] 82, 232 (1910); [2] 
83, 210 (1911); Ann. chim. phys. [8] 20, 445 (1910). 

2 J. Chem. Soc. 66, 843 (1894); Ber. 10, 1485 (1877); 15, 1820 (1882); 16, 696, 
1632 (1883). 

3 Bull. soc. chim. [2] 35, 505 (1881); [3] 17, 969 (1897); Ann. chim. phys. [6] 
14, 447 (1888); Monatsh. 32, 639 (1911); J. Am. Chem. Soc. 43, 1965 (1921). 

4 J. prakt. Chem. [2] 33, 319 (1886); [2] 41, 4 (1890); Ann. 234, 239 (1886); 
299, 300 (1898); 311, 180 (1900); Ber. 28, 1134 (1895); 41, 3632 (1908); J. Russ. 
Phys. Chem. Soc. 46, 1067 (1914). 

6 J. Am. Chem. Soc. 43, 1922 (1921). 

8 Anthracene and Anthraquinone, pp. 130-141, Van Nostrand (1921). 

7 Ber. 45, 796 (1912). 

8 Ber. 46, 1214 (1912). 
Ber. 46, 1646 (1913). 



XVII 

/3-METHYL ESCULETIN 
(6, 7-Dihydroxy-4-methyl-l, 2-benzopyrone) 



OCOCHs 
OCOCHs 




CH 3 COCH 2 C02C 2 H5 + 2H 2 



OCOCH 3 CH 3 

I 
HO 




3 CH 3 C0 2 H + C 2 H 5 OH 

// 



Prepared by E. B. VLIET. 

Checked by ROGER ADAMS and E. E. DREGER. 

1. Procedure 

A SMOOTH, uniform paste is made by thoroughly mixing 60 g. 
of ethyl acetoacetate (Note i) and 114 g. of hydroxyhydro- 
quinone triacetate (p. 35). This requires several minutes of 
stirring. To this mixture is added 450 cc. of 75 per cent sul- 
furic acid (Note 2). The paste slowly dissolves with the evolu- 
tion of heat, giving a deep red solution; the latter is heated on 
a warm bath with occasional stirring until it reaches 80, at 
which temperature it is maintained for one-half hour. It is 
then allowed to cool to room temperature and poured into 
1850 cc. of cold water. The resulting mixture is cooled to room 
temperature, filtered with suction, and the precipitate washed 
with cold water to free it from excess acid. The /3-methyl 
esculetin thus obtained is dried at 100 and is generally gray in 
color. The yield is about 80 g. (92 per cent of the theoretical 
amount). 

45 



46 * ORGANIC SYNTHESES 

A pure product may be obtained by dissolving with the aid 
of heat and stirring 100 g. of /3-methyl esculetin in a solution of 
200 g. of borax in 700 cc. of water. The solution obtained is 
filtered while hot and then cooled, whereupon the esculetin 
borate separates (Note 3). This is filtered off and dissolved in 
1800 cc. of water, and the solution thus obtained added to 50 g. 
of concentrated sulfuric acid in 500 cc. of water. /3-Methyl 
esculetin separates and, after the mixture has been cooled, is 
tillered, washed, and dried. From 100 g. of the crude material, 
85 g. of pure product melting at 272-274 (uncor.) is obtained. 
This is generally nearly colorless but occasionally possesses a 
slight grayish tinge. 

2. Notes 

1. In order to obtain a fairly pure product without recrys- 
tallization, the intermediate ethyl acetoacetate and hydroxy- 
hydroquinone triacetate must be pure. 

2. It is important to use 75 per cent sulfuric acid in this 
reaction, because more concentrated acid gives a very dark 
product and a lower yield, while more dilute acid will not induce 
the reaction. 

3. The exact nature of the precipitate has nol been deter- 
mined. 

3. Other Methods of Preparation 

/3-Methyl esculetin was first prepared by Pechman, 1 by con- 
densing hydroxyhydroquinone triacetale and ethyl acetoacetate 
by allowing them to stand for twenty-four hours with cold con- 
centrated sulfuric acid. This method gave a dark product, 
difficult to purify, and a yield of 60-65 P er cent. Pechman also 
used boiling alcoholic zinc chloride as the condensing agent in 
place of sulfuric acid but does not state the yield thus obtained. 

Bargellini and Martegiani ~ used 73 per cent sulfuric acid 
and heated on the water bath. They obtained an improved 
yield of a product of better quality. Zinc chloride in acetic 
acid proved to be unsatisfactory. 

^er. 34, 423 (1901). 

2 Gazz. chim. ital. 41 (2), 613 (1911). 



XVIII 

METHYLENE AMINOACETONITRUE 
(a-Hydroformamine Cyanide *) 

NaCN+NH 4 Cl + 2 HCHO -> CH2=NCH 2 CN+NaCl+2H 2 

Prepared by ROGER ADAMS and W. D. LANGLEY. 
Checked by H T. CLARKE and E. R, TAYLOR. 

1. Procedure 

IN a 5-!. round-bottom flask, fitted with a mechanical stirrer 
and surrounded by an ice-salt bath, are placed 1500 cc, of tech- 
nical formaldehyde (sp. gr. 1.078/20) (Note i) and 540 g. of 
ammonium chloride. A thermometer is placed in the liquid, 
which is cooled to o. This temperature is maintained through- 
out the entire reaction (Note 2). Stirring is commenced 
(Note 3) and a solution of 490 g. of 98 per cent sodium cyanide 
in 850 cc. of water is dropped into the mixture of ammonium 
chloride and formaldehyde at such a rate (about 90 drops per 
minute) that at least six hours will be required for this addition. 

When one-half the sodium cyanide solution has been added, 
all of the ammonium chloride will be in solution. At this point, 
the addition of 380 cc. of glacial acetic acid is started at such a 
rate (2 to 2.5 cc. per minute) that the addition of both the acid 
and the remainder of the sodium cyanide solution will be com- 
pleted at the same time. The methylene aminoacetonitrile 
begins to separate in white crystals shortly after the addition of 
the glacial acetic acid has commenced. After all the sodium 
cyanide solution and acetic acid have been added, the mixture 
is stirred for an hour and a half longer; then the precipitate 

* The actual molecular formula is C 9 Hi 2 N 6 . Johnson and Rinehart, J. Am. 
Chem. Soc. 46, 768, 1653 (1924). 

47 



48 * ORGANIC SYNTHESES 

is filtered off, transferred to a beaker, and stirred with 1.5 1. 
of water. The product is filtered with suction, washed with 
500 cc. of water (Note 4), and dried on filter paper. The yield 
is 410 to 475 g. (64-74 per cent of the theoretical amount) of a 
product of which the melting point is 129 (Note 5). 

2. Notes 

1. The formalin contains 35 per cent formaldehyde by weight, 
as determined by specific gravity. It should contain no sus- 
pended paraformaldehyde. 

2. During the reaction, the temperature should be kept as 
near o as possible and should never rise above 5. If the 
temperature goes higher, a heavy oil is sometimes obtained 
instead of the crystalline product. It is not difficult to main- 
tain the low temperature when the formaldehyde and ammo- 
nium chloride are cooled to o before any of the sodium cyanide 
is added. 

3. In order to obtain good yields, the stirring must be vigor- 
ous throughout the entire reaction. 

4. With careful washing, 500 cc. of cold water should be 
sufficient to remove all chlorides. 

5. For most purposes, the product is pure enough as it is 
obtained from the reaction mixture, but it may be crystallized 
from water. This recrystallization is, however, attended with 
considerable loss. 

3. Other Methods of Preparation 

Methylene aminoacetonitrile has been prepared by the 
action of formaldehyde on aminoacetonitrile, 1 and by the action 
of formaldehyde on a mixture of ammonium chloride, potassium 
cyanide, and acetic acid. 2 

1 J. prakt. Chem. (2) 65, 192 (1902). 

2 Ber. 27, 59 (1894); 36, 1507 (1903); 43, 868 (1910); J. Am. Chem. Soc. 768, 
1653 (1924). 




XIX 
NICOTINIC ACID 



TT 

CioH 14 N 2 + (HN0 3 ) ' ' 2tl 



Prepared by S. M. MCELVAIN. 

Checked by J. B. CON ANT and B. B. CORSON. 

1. Procedure 

IN a 5-!. round-bottom flask is placed 4 kg. of C.P. concen- 
trated nitric acid (sp. gr. 1.42) (Note i). To this is added, in 
25-cc. portions, 210 g. of nicotine (Note 2). The addition should 
be made carefully in order that local heating may not occur and 
material be lost. After each addition of nicotine, the flask 
should be shaken in order to insure a homogeneous solution. 
The addition of the nicotine causes the temperature of the liquid 
to rise somewhat but not sufficiently to cause evolution of nitro- 
gen dioxide. The flask is placed on a steam bath under a hood 
and heated until the liquid reaches a temperature of 70. It is 
then removed and the reaction allowed to continue spontane- 
ously (Note 3), heat enough being evolved to cause the liquid to 
boil. The boiling ceases after one hour but the flask is replaced 
upon the steam bath for ten to twelve hours, during which time 
there is a more or less continuous evolution of oxides of nitrogen. 

The contents of the flask are then poured into an evaporat- 
ing dish and evaporated almost to dryness on the steam bath 
(about ten hours). The purification which follows is best 
carried out with the product of two runs such as have been 
described above. 

After the evaporation of most of the liquid, the nicotinic 
acid nitrate from two runs is transferred to a 1.5-!. beaker, 
400 cc. of distilled w r ater is added (Note 4) and the mixture is 
heated until complete solution results. On cooling, the nico- 
tinic acid nitrate separates as yellow granular crystals and is 

49 



50 ORGANIC SYNTHESES 

filtered off. To obtain it absolutely pure, it may be recrystal- 
lized in a way similar to that just described but with the use of 
bone-black. It contains one molecule of water of crystalliza- 
tion and has a melting point of 190-192 (cor.). The yield is 
420-460 g. (85-91 per cent of the theoretical amount). 

The 420-460 g. of crude nicotinic acid nitrate from two runs 
(not necessarily dry) is dissolved in 900 cc. of boiling water in a 
3-1. beaker and 800 g. of crystalline disodium phosphate 
(Na 2 HP04- i2HoO) added with constant stirring. The result- 
ing thick mixture is stirred and heated almost to boiling for five 
minutes and then allowed to cool. The mixture is finally chilled 
to o by an ice bath. It is well to stir occasionally during the 
crystallization to prevent the formation of too solid a cake of 
crystalline material. The nicotinic acid is filtered off upon a 
i5-cm. Buchner funnel and washed with three zoo-cc. portions 
of cold water. 

The yield is 260-300 g. of material containing a small amount 
of mineral salts but otherwise nearly pure. It can be purified 
further by recrystallization from 2.5 to 3.5 1. (Note 4) of hot 
water, 150-180 g. of material, which melts at 230-232 (cor.), 
being obtained. The yield of recrystallized material is 50-60 
per cent of the theoretical amount, based upon the nicotine em- 
ployed. 

The recrystallization is the least satisfactory part of this 
procedure and involves the greatest apparent loss of material; 
the product before recrystallization is sufficiently pure for most 
purposes. By evaporation of the mother liquors, 40-45 g. of 
pure nicotinic acid may be obtained, making the total yield of 
pure material 190-225 g. (63-74 per cent of the theoretical 
amount); in addition, a small amount of somewhat less pure 
material is recovered. 

2. Notes 

1. Fuming nitric acid, the use of which is advised in the 
literature, is not as convenient to use and gives no better results 
than concentrated nitric acid. 

2. A product of loo per cent purity gives no better results 



NICOTINIC ACID 51 

than does the crude 95 per cent material used in this experiment. 
The nicotine was purchased from the Hall Tobacco Company, 
of St. Louis, Mo. 

3. If the nicotine and nitric acid mixture is merely placed on 
a steam bath and allowed to heat without control of the tempera- 
ture, an occasional run will react violently, with loss of material. 

4. The amounts of solvent given for the various recrystal- 
lizations are those which give best yields and it is advisable to 
follow them as closely as possible. 

5. Nicotinic acid hydrochloride may be obtained directly 
from the nitrate by heating on a steam bath 460 g. of crude 
nitrate with 1000 cc. of concentrated hydrochloric acid (sp. gr. 
1.19). After six to eight hours, the evolution of gas ceases and 
the liquid is evaporated under diminished pressure. The dry 
salt is again treated with 500 cc. of hydrochloric acid and heated 
for five hours and then evaporated as before. 

After the salt has been again obtained, it is dissolved in 400 cc. 
of hot water and the solution diluted with four times its volume 
of 95 per cent alcohol. Upon cooling and stirring, the hydro- 
chloride, melting at 273-274, is obtained in a yield of 245- 
250 g. An additional quantity of 75-80 g. may be obtained 
from the mother liquors. 

3. Other Methods of Preparation 

Nicotinic acid has been prepared by the oxidation of nicotine 
with nitric acid. 1 It has also been prepared by the action of 
potassium permanganate upon /3-picoline, nicotine, lutidine, 
0-phenyl pyridine, and -dipyridyl 2 and by the action of 
chromic acid upon nicotine and 0-phenyl pyridinecarboxylic 
acid. 3 

It may also be obtained by heating quinolinic acid 3 and 
certain other pyridine dicarboxylic acids. 2 The nitrile has been 
prepared by heating sodium /3-pyridinesulfonate with potassium 
cyanide. 4 

1 Ann. 166, 330 (1873); Ber. 34, 702 (1901); Chem. Zentr. 1898 (I), 677, 
2 Beilstein 4, 143 (1899); 4*, 108 (1906). 

3 Rec. trav. chim. 1, 121 (1882); Arch. Pharm. 240, 353 (1902). 

4 Ber. 15,63 (1882). 



XX 

PENTAERYTHRITOL 

(Tetra-hydroxymethyl methane) 

8CH 2 O+2CH 3 CHO+Ca(OH) 2 - 2C(CH 2 OH) 

Prepared by CHEMICAL LABORATORY, PICATINNY ARSENAL. 
Checked by H. T. CLARKE and Ross PHILLIPS. 

1. Procedure 

IN a 6-gal. crock provided with an efficient stirrer are placed 
10.5 1. of water, 5600 g. commercial (35-40 per cent) formalde- 
hyde, and 630 g. of acetaldehyde (b.p. 20-22). To this mix- 
ture is added, during the course of one-half hour, with constant 
mechanical stirring, 475 g. of high-grade quicklime to which 
enough water has been added to cause the disintegration of 
lumps by slaking. This lime must be in the form of a fine 
powder (Note i). During the addition, the temperature of the 
mixture is raised by injection of live steam (Note 2) to 60-65, 
and is held at this point for two hours after all has been added 
(Note 3). 

The mixture is then cooled by surrounding the crock with 
cold water, and about 1700 g. of cold 50 per cent sulfuric acid is 
added, until a filtered sample just fails to yield a further precipi- 
tate of calcium sulfatc upon the further addition of sulfuric acid. 
The calcium sulfate is filtered off and washed with cold water. 
A saturated aqueous solution of oxalic acid is cautiously added 
to the filtrate until a filtered sample gives no test for calcium 
salts in solution (Note 4). 

The resulting solution, which should now be clear and lemon 
yellow in color (Note 5) , is concentrated under reduced pressure 
on the steam bath (Note 6, Fig. 3) until the volume is reduced 

53 



54 



ORGANIC SYNTHESES 



to 3.5-4 1. It is then cooled and the crystalline precipitate 
filtered off by suction and washed with methyl alcohol or 95 
per cent ethyl alcohol (Note 7) in small portions, until the wash- 
ings are colorless. The product thus obtained weighs 900-960 g. 
and melts without decomposition at 250-252 (Note 8). The 
mother liquor and washings are further concentrated (Note 9) 
to a syrup, from which a second crop of 100-250 g. is obtained 
upon cooling. This is washed as before with alcohol but pos- 




To Pump 



FIG. 3. 



sesses a slightly yellow color and must be recrystallized from 
an equal weight of water. The total yield of product of m.p. 
250-252 is 975-1055 g. (50-54 per cent of the theoretical 
amount) . 

2. Notes 

1. The quicklime may be ground mechanically before addi- 
tion, but this is less convenient than disintegrating it by the 
cautious addition of water. 

2. If mechanically powdered quicklime is used, the use of 
steam is unnecessary, and the temperature is to be controlled 



PENTAERYTHRITOL 55 

by the rate of addition. The use of heating and cooling coils 
in the crock is most convenient if available; such coils may 
safely be of iron tubing. Temperatures above 65 result in a 
lower yield of less pure product. 

3. After the mixture has been maintained at 60-65 for a 
period of about one hour, the initial gray color undergoes a rapid 
change to yellow. This change is accompanied by a marked 
diminution in the odor of aldehydes. 

4. The presence of only a slight excess of oxalic acid is per- 
missible, although it is essential to, remove all calcium salts 
since they would contaminate the final product; but small 
quantities of free oxalic acid do not interfere with the subsequent 
operations and are removed in the mother liquors. 

5. The liquor may profitably be treated with decolorizing 
carbon at this point. 

6. The apparatus shown in Fig. 3 has been found convenient 
for such evaporations under reduced pressure. The distillation 
is started with 3.5-4 1. in the 12-!. flask, and the level of liquid 
is maintained by controlling the rate of addition by means of a 
screw clamp. A 2-1. flask has been found satisfactory for the 
condensing intermediate receiver, provided the outside be com- 
pletely wetted by the cold water. 

7. Nearly i 1. of ethyl alcohol is required. Pentaery- 
thritol is insoluble in the cold alcohol, which dissolves the sticky 
polymerized aldehydes obtained on concentrating the solution. 

8. The product is sufficiently pure for most purposes, but 
may be recrystallized from slightly more than an equal weight 
of boiling water. 

9. The washings may be collected separately and the alcohol 
recovered by distillation from a steam bath under slightly reduced 
pressure. 

3. Other Methods of Preparation 

The only practicable process for the preparation of pentaery- 
thritol consists in condensing acetaldehyde with formaldehyde 
in dilute aqueous solution by means of calcium (or 



56 ORGANIC SYNTHESES 

hydroxide; l it has, however, also been formed by the action 
of sodium amalgam upon the pentaerythrose produced by con- 
densing acetaldehyde with formaldehyde by means of sodium 
hydroxide. 2 

i Ann. 265, 316 (1891); Ann. 276, 58 (1893); C. A. 11, 2543 (1917); D. R. P. 
390,622; Chem. Zcntr. 1924 (i) 2396. 
2 Am.Chem. 1.37,38(1907). 



XXI 
0-PHENYLHYDROXYLAMINE 

2Zn+H 2 O -> C G H 5 NHOH + 2ZnO 

Prepared by OLIVI R KAMM. 
Checked by C S MARVKL. 

1. Procedure 

IN a 4-gal. earthenware jar are placed 250 g. of technical 
ammonium chloride, 8 1. of water, and 500 g. of nitrobenzene. 
The mixture is stirred vigorously by means of a mechanical 
stirrer, and 020 g. of zinc dust of 85 per cent purity is added 
(Note i) during the course of fifteen to twenty minutes (Note 
2). As the reduction proceeds, the temperature rises to 6065. 
Stirring is continued for fifteen minutes after all the zinc dust 
has been added, at the end of which time the reaction is com- 
plete, as indicated by the fact that the temperature of the mix- 
ture ceases to rise. 

While still hot, the solution is filtered with suction in order 
to remove the zinc oxide, which is washed with i 1. of hot water. 
The filtrate is placed in an enamelled pan, saturated with salt, 
about 3 kg. being required, and cooled to o by being placed in 
an ice-salt mixture. The phenylhydroxylamine, which crystal- 
lizes out in long, light yellow needles (Note 3), is filtered by 
suction. The yield of crude product varies considerably, 
depending upon the amount of salt solution present, but aver- 
ages 350-400 g. This corresponds to 275-300 g. (62-67 P er cent 
of the theoretical amount) of actual phenylhydroxylamine, as 
determined by its separation from inorganic materials by solu- 
tion in ether (Note 4). 

Since phenylhydroxylamine deteriorates upon storage, it is 
generally used promptly, as illustrated in the preparation of 
cupferron, p. 19. The oxalate is somewhat more stable. 

57 



58 ORGANIC SYNTHESES 

2. Notes 

1. The zinc dust must be analyzed (Gattermann, " Practical 
Methods of Organic Chemistry/' 3rd ed., p. 390), and a propor- 
tional quantity used if the zinc content is not 85 per cent. 
Technical nitrobenzene is satisfactory if it distils over a range 
of not more than 5 degrees and is not acid in reaction. 

2. When the reaction is run more slowly, the temperature 
does not reach 60-65 and the yield is poorer. At 50-55, the 
yield is about 55 per cent. 

3. It is important that the phenylhydroxylamine solution be 
kept at o for at least one-half hour or considerable material will 
be lost in the solution. The use of an enamelled pail saves a 
great deal of time at this step. 

4. Phenylhydroxylamine is soluble in saturated salt solution 
at o to the extent of about 9 grams per liter, but this amount is 
not included in the yields given. Occasional yields of 300- 
310 g. of dry phenylhydroxylamine have been obtained. 

3. Other Methods of Preparation 

Although phenylhydroxylamine may be prepared by catalytic 
reduction, 1 by the oxidation of aniline, 2 and by electrolytic reduc- 
tion of nitrobenzene, 3 the most feasible method is still based 
upon the original zinc reduction method of Bamberger 4 and of 
Wohl. 5 Various solvents and catalysts have been used in this 
reduction, and copper-coated and amalgamated zinc, as well as 
aluminium amalgam, 6 have been substituted for zinc dust. 
The method herein recommended is essentially one previously 
described 7 but it has been found 8 that cooling is not an essential, 
as claimed in the patents. The preparation of the oxalate is 
also a more recent contribution. 9 

1 Ber. 55B, 875 (1922). 2 Ber. 32, 1676 (1899). 

3 Chem. Zentr. 1898 (II), 634; Z. physik. Chem. 32, 272 (1900); J. Phys. Chem. 
19, 696 (1915). 

4 Ber. 27, 1348, 1548 (1894). 6 Ber. 27, 1432 (1894). 
6 Beilstein 2*, 241 (1903); J. Chem. Soc. 119, 767 (1921); J. Ind. Eng. Chem. 

12, 799 (1920). 

7 D R. P. 89,978; Frdl. 4, 47 (1896). 8 J. Am. Chem. Soc. 41, 277 (1919). 
9 U. S. Patent 1,390,260; C. A 16, 105 (1922). 



XXII 
n-PROPYLBENZENE 



C 6 H6CH 2 Cl+Mg 

C6H 5 CH 2 MgCl+(C 2 H 5 )2SO4 -> 

C 6 H 5 CH 2 CH 2 CH 3 +MgCl(SO4C 2 H 5 ) 

Prepared by HENRY OILMAN and C. H. MEYERS. 
Checked by C. S. MARVEL and H. O. CALVERY. 

1. Procedure 

IN a 5-!. flask standing in an empty water bath are placed 
50 g. of clean magnesium turnings and 600 cc. of dry ether 
which has been distilled over phosphorus pentoxide and stored 
over sodium; the flask is then fitted with a stirrer having a 
mercury seal, a thermometer, an efficient reflux condenser, and 
a dropping funnel. About 50 cc. of a solution of 253 g. of benzyl 
chloride, boiling at 172-175, in 800 cc. of dry ether is then 
added through the dropping funnel and the mixture heated just 
to boiling by placing in the bath enough water at 40 to cover 
about half the surface of that part of the flask which is in con- 
tact with the ethereal mixture. 

As soon as the ether begins to boil, the warm water is siphoned 
out; if the boiling should continue vigorously, owing to the 
reaction having set in, the rate may be regulated by placing 
cold water in the bath. The remainder of the benzyl chloride 
solution is then added at such a rate that the mixture boils 
gently; this will require about four hours. When all has been 
added, stirring is commenced and the mixture gently boiled for 
fifteen minutes by the gradual replacement of the cold water by 
warm. 

59 



60 ORGANIC SYNTHESES 

The temperature of the mixture is then lowered by means of 
running water, and 385 g. of c. p. ethyl sulfate (Note i) is 
dropped in, with continuous stirring, during one and a half 
hours, allowing the temperature to rise gradually. When all 
has been added, stirring is continued with gentle boiling for an 
hour. The cooled mixture is then poured cautiously, with 
stirring, upon a mixture of i kg. of crushed ice, i kg. of water, 
and 200 cc. of concentrated hydrochloric acid. 

After a few minutes, the bulk of the water layer is removed 
by a siphon and the clear ethereal solution decanted, so far as 
possible, into a 2-1. flask. The remaining mixture is filtered 
through a glass-wool plug into a separatory funnel, and after 
removal of the aqueous portion, the remaining ethereal solution is 
added to that in the flask. An efficient fractionating column 
is attached, and the ether distilled on the water bath; the resi- 
due is then fractionated and collected as pure w-propylbenzene 
boiling at 154-158. The yield is 133-156 g. (55-65 per cent 
of the theoretical amount). 



2. Notes 

i. The technical grade of diethyl sulfate gives poorer yields 
on account of the presence of free acid. The c. P. grade was 
used in order to obtain the results given in the procedure. 



3. Other Methods of Preparation 

w-Propylbenzene has been prepared by the action of sodium 
on a mixture of propyl bromide and bromobenzene, 1 of zinc 
dust upon a benzene solution of allyl bromide, 2 and of zinc ethyl 
upon benzyl chloride; 3 and aluminium chloride has been 
employed to condense benzene with propyl bromide, 4 allyl 

'Ann. 149, 324(1869). 

2 Jahresb. 1806, 1516; Bull. soc. chim. (3) 16, 126 (1896). 
3 Ber. 10, 294 (1877); Gazz. chim. ital. 7, 21 (1877). 

4 Ber. 24, 768 (1891); J. Russ. Phys. Chem. Soc. 27, 457 (1895); Bull. soc. 
chim. (3) 16, 864 (1896). 



w-PROPYLBENZENE 61 

chloride 5 and trimethylene bromide, 6 but the tendency of this 
reagent to induce isomerization is a distinct danger. 

tt-Propylbenzene has also been obtained by the action of hot 
sulfuric acid upon a mixture of propyl alcohol and benzene. 7 
Reduction methods have been applied to various monosub- 
stituted benzene derivatives possessing a three-carbon-chain, 
namely, phenyl ethyl ketone and benzyl methyl ketone, 8 
7-phenyl ;z-propyl chloride or bromide, 9 propenylbenzene, 10 
phenyl ethyl ketoxime n and cinnamyl alcohol or phenyl allyl 
alcohol. 12 

5 Ann. 218, 379 (188.3); Bull soc. chim. (2) 41, 197 (1884); (2) 43, 588 (1885). 

6 Compt. rend. 132, 155 (IQOI) 

7 Compt rend 117, 236 (1893). 

8 J. prakt. Chem (2) 81, ^87 (IQTO); Rer 40, 1830 (1013). 

Ber 43, 178 (IQIO), 44, 2872 (IQII); 45, 2176, 2179 (1912). 
10 Ber. 36, 622, 773 (1903) 

11 Bull. soc. chim. (4) 9, 465 (1911). 

12 Ber. 39, 2590 (1906). 



XXIII 

PYRUVIC ACID 
CHOHCOaH 



| +(KHSO 4 ) 

CHOHCO 2 H 

Prepared by J. W. HOWARD and W A FRASER. 
Checked by C S MARVEL and R L SHRINER. 

1. Procedure 

AN intimate mixture of 600 g. of finely powdered freshly 
fused potassium acid sulfate and 400 g. of powdered tartaric acid, 
prepared by grinding them together in a mortar, is placed in a 
3-1. round-bottom Pyrex flask connected with a condenser which 
is rilled with water but does not have any water flowing through 
it. The mixture is heated by means of an oil bath maintained 
at a temperature between 210 and 220 until liquid no longer 
distils over. Some foaming takes place (Note i), but if fused 
potassium acid sulfate is used and the temperature of the bath 
does not rise above 220, it is not difficult to control. The dis- 
tillate is then fractionated under reduced pressure. Pyruvic 
acid passes over at 75-80; 25 mm. and the yield is 117-128 g. 
(50-55 per cent of the theoretical amount). 

2. Notes 

1. If the mixture foams badly, it may be kept from frothing 
over by heating the upper part of the flask with a free flame. 

2. The cake left in the reaction flask may be removed readily 
by inverting over a steam jet. 

3. Other Methods of Preparation 

Pyruvic acid has been prepared from ,a-dichloropropionic 
acid and from the corresponding dibromo acid, by heating with 

63 



G4 ORGANIC SYNTHESES 

water under pressure, by heating with barium hydroxide solu- 
tion, and by the treatment of the aqueous solutions with silver 
oxide or silver carbonate. 1 The action of sodium hydroxide on 
a,a-dibromopropionic acid has also been studied. 2 Better 
results have been reported from the hydrolysis of acetyl cyanide 
and of oxalacetic ester. 3 

It has been obtained by the oxidation of lactic acid, 4 mesa- 
conic acid and citraconic acid, 5 acetone and acetol, 6 but in 
general these oxidation procedures are not suitable as prepara- 
tive methods. 

Pyruvic acid may be obtained by the distillation of tartaric 
acid or gly eerie acid. 7 Better results are obtained, however, by 
the distillation of tartaric acid in the presence of a dehydrating 
agent such as potassium bisulfate. 8 This method has been 
adopted after a study of a variety of dehydrating agents and 
various experimental procedures. 

1 Ber. 5, 477 (1872), 10, 264, 2037 (187?), 18, 228, 235 (1885). 

2 Ann. 342, 132 (1905). 

3 Ber. 11, 620, 156.3 (1878), Ann. 240, 327 (1888). 

4 J. Chem. Soc 77, 71 (1900); Ber. 17, 840 (1884); Chem. Met Eng 28, 357 

(1923). 

5 Ann. 305, 48, 49 (1899). 

6 Compt rend. 140, 1592 (1905), Bull soc. chirn. (4) 3, 250 (1908); Ber. 20, 
641 (1887); J. Am Chem Soc 3, 2661 (1917). 

7 Ann physik (2)30,1(1835), Ann 131,338(1864), 188,314(1877). 

8 Ber. 14, 321 (1881); Bull, soc chim (3)13,335(1895), Rec trav. chirn. 19, 
278 (1900), Ann. 242, 269 (1887); Ber. 43, 2188 (1910). 



XXIV 
SODIUM />-HYDROXYPHENYLARSONATE 



Prepared by W G CHRISTIANSEN and A. J. NORTON. 
Checked by OLIVER KAMM. 

1. Procedure 

SEVEN HUNDRED AND TWENTY grams of syrupy arsenic acid 
(75-80 per cent) is boiled in a beaker until the temperature of 
the acid is 150; about 120 g. of water is driven off, leaving a 
syrup containing approximately 95 per cent of orthoarsenic 
acid, which is then added to 300 g. of phenol in a i-l. round- 
bottom, short-neck Fyrex flask. By means of a 3-hole stopper, 
an efficient jacketed stirrer (Org. Syn. i, 4) and a thermometer 
are introduced into the flask, and a connection is established 
with a downward condenser. The flask is set in an oil bath 
which is heated at once to 155-160, and the stirrer is run at a 
rate high enough to insure thorough mixing. 

When the inside temperature reaches 140, boiling com- 
mences and water plus a very little phenol begins to distil. 
The distillation is allowed to continue until 60 cc. (one molecular 
equivalent) of water has been collected; this usually requires 
one hour, and the inside temperature rises to 146. The down- 
ward condenser is then replaced by a reflux condenser (Note i) 
and the reaction is allowed to continue until a total of four 
hours has elapsed from the time the contents of the flask first 
reached 140. After the return condenser has been attached, 
the inside temperature declines slowly to 141 or 142 and the 
reaction mixture becomes thicker and somewhat tarry. After 
the contents of the flask have been partially cooled, they are 

65 



66 . ORGANIC SYNTHESES 

* 

poured into 4 1. of water and mechanically stirred; the agitation 
is continued for a short time in order to break up the tarry 
material and enable the water to dissolve the hydroxyphenyl- 
arsonic acids completely. 

Finely ground barium hydroxide is added gradually to the 
well-stirred water solution until the material is slightly alkaline 
to litmus, in prder to remove the excess of arsenic acid; when 
this point is reached, the solution becomes pink. If the pro- 
cedure is carried out properly, 700-800 g. of Ba(OH) 2 8H2O 
should suffice (Note 2). The time required by this method is 
greater than when a hot solution of barium hydroxide is used, 
but the method is more convenient and does not cause such a 
great increase in volume. After removal of the barium arsenate 
by filtration, the mother liquor and washings are treated with 
sulfuric acid until the solution contains neither barium nor 
sulfate ions. When the barium sulfate has been separated and 
thoroughly washed (Note 3), the filtrate is concentrated on a 
steam bath to about 3 1., neutralized to litmus with sodium 
hydroxide, filtered, evaporated until the solution becomes well 
coated with crystals, and then treated with 2.5 volumes of alcohol. 
After the mixture has cooled in an ice-box, the sodium />-hydroxy- 
phenylarsonate is separated, washed with alcohol, and dried in 
an oven at 80. A second crop may be secured from the filtrate 
by concentrating it further and precipitating with alcohol. 
The total yield of anhydrous sodium />-hydroxyphenylarsonate 
is 252 g. (33 per cent of the theoretical amount). By proper 
manipulation, it is possible to obtain as much as 240 g. in the 
first crop and to have it free from sulfate, arsenate, and sodium 
0-hydroxyphenylarsonate which is one of the by-products formed 
in this reaction (Note 4). 

2. Notes 

i. When the downward condenser is not replaced by a reflux 
condenser, the total volume of water that distils is 90-120 cc. 
and the mass becomes very tarry, owing to the oxidation of 
phenol or of some intermediate substance formed in the reaction. 



SODIUM />-HYDROXYPHENYLARSONATE 67 

/>-Hydroxyphenylarsonic acid is not destructively oxidized by 
hot arsenic acid. 

2. In removing the excess arsenic acid with barium hydroxide, 
the solution should not be permitted to become strongly alka- 
line, as the barium salt of the hydroxyphenylar sonic acid may 
commence to separate, thereby decreasing the yield. 

3. The filtration of large quantities of barium sulfate is 
usually tedious; but if filtering carbon is added to the suspension 
to be filtered and if a mat of this carbon is prepared on the filter 
by filtering an aqueous suspension of carbon, the barium sulfate 
may be removed rapidly and completely, even when it is pre- 
cipitated from cold solutions. 

4. When phenol is arsonated with arsenic acid, small amounts 
of 0-hydroxyphenylarsonic acid, /?,//-di-hydroxyphenylarsinic 
acid and 0,//-di-hydroxyphenylarsinic acid are formed as by- 
products. As the sodium salts of the secondary acids are soluble 
in alcohol, they will not appear in the material precipitated by 
the addition of alcohol. The sodium salt of 0-hydroxyphenyl- 
arsonic acid, although insoluble in alcohol, will not be precipi- 
tated if the solution is not concentrated too far before addition 
of the alcohol. To test the material for the presence of the 
ortho compound, ferric chloride is added to an aqueous solution 
of a small amount of the solid; the ortho hydroxy acid gives a 
deep purple color, whereas the para acid gives no coloration. 
The sodium salt which is precipitated with alcohol contains 
water of crystallization, which is driven off by drying at 80. 
The product can be purified by dissolving in hot water and adding 
hot alcohol until a slight permanent turbidity is produced. 
Upon cooling, the material separates in a crystalline condition. 
Occasionally, the second crops of sodium />-hydroxyphenyl- 
arsonate contain small amounts of arsenious oxide which is 
formed from the arsenic acid during the oxidation mentioned 
above. 

3. Other Methods of Preparation 

/>-Hydroxyphenylarsonic acid may be prepared by diazotiza- 
tion of arsanilic acid and replacement of the diazo group by 



68 ORGANIC SYNTHESES 

* 
hydroxyl. 1 The method of directly introducing the arsenic 

acid group into phenol is more satisfactory. This preparation 
was first described in the patent literature, 2 but the method 
proved unworkable and was reinvestigated and improved by 
Conant 3 and later by Jacobs and Heidelberger. 4 In the present 
method, 5 additional improvements have been effected. 

!Ber. 41, 1854 (iqo8). 

2 D. R. P. 205,616; Frdl. 9, 1040 (igo8). 

3 J. Am. Chem. Soc. 41, 431 (IQIQ) 

4 J. Am. Chem. Soc. 41, 1440 (IQIQ). 

5 J. Am. Chem. Soc. 45, 2188 (1923). 



XXV 

o-TOLUNITRILE AND />TOLUNITRILE 
CH 3 C ti H 4 NH 2 +HN0 2 +HCl 



CH 3 C6H 4 N2Cl+NaOH+NaCu(CN)2 -> 

CH 3 C G H 4 CN+N2+NaCl + CuCN 

Prepared by H. T CLXRKK and R. R. READ. 
Checked by C S. MARVEL and M. M BRUBAKER. 

1. Procedure 

A. Preparation of the cuprous cyanide solution: Cuprous 
chloride prepared from 1250 g. of copper sulfate, according to 
the directions given in Org. Syn. 3, 33, is suspended in 2 1. of 
cold water in a 15-!. crock fitted with a mechanical stirrer. A 
solution of 050 g. of sodium cyanide (96-98 per cent) in i 1. of 
water is added and the mixture stirred, whereupon the cuprous 
chloride enters into solution with considerable evolution of heat 
(Note i). The mixture is then cooled by surrounding the crock 
with cold water (Note 2). 

B. Preparation of o-tolunilrilc: While the cuprous cyanide 
solution is cooling, 428 g. of 0-toluidinc is mixed in a 20-!. crock 
with T 1. of commercial 28 per cent hydrochloric acid (sp. gr. 
1.14) and enough cracked ice, about 4 kg., to bring the tempera- 
ture of the mixture to o. A solution of 280 g. of sodium nitrite 
in 800 cc. of water is added, with stirring, to the resulting suspen- 
sion of 0-toluidine hydrochloride, the temperature being kept at 
05 by the addition of cracked ice. The addition of the nitrite 
occupies about fifteen minutes; at the end of the operation, the 
mixture must show a distinct and permanent reaction for free 
nitrous acid on testing with starch iodide paper (Note 3). The 
final volume of the solution is 5-6 1. The mixture is now 

69 



70 ORGANIC SYNTHESES 

cautiously neutralized by adding dry sodium carbonate with 
constant stirring, using litmus paper to determine the end point; 
about 200 g. of the anhydrous carbonate is required (Note 4). 

The cold cuprous cyanide solution is now chilled to 0-5 by 
the addition of ice, and i 1. of benzene is poured on the surface. 
To this mixture is slowly added the cold neutralized diazonium 
solution. During the addition, which occupies about thirty 
minutes, such vigorous stirring is maintained that the benzene 
on the surface is constantly drawn to the stirrer, and the tempera- 
ture is maintained at 0-5 by occasionally adding ice. As soon 
as the diazonium solution comes into contact with the cuprous 
cyanide, a dark yellow, oily precipitate is formed which at once 
begins to give off nitrogen; the resulting nitrile is taken up by 
the benzene as soon as it is formed (Note 5). When all has 
been added, the temperature is held at 0-5 for thirty minutes 
longer, and then is allowed to rise to that of the room (20-25), 
which usually requires about three hours. 

After stirring has been continued for two hours longer, the 
crock is surrounded by hot water or steam and warmed to 50 
without stirring. The mixture is then allowed to stand until 
cool, when the aqueous layer is drawn off by means of a siphon. 
The upper oily layer is transferred to a 12-!. flask and distilled 
in a current of steam until no more oil passes over; about 10 1. 
of distillate is collected (Note 6). The water is drawn off and 
the benzene removed by distillation, by means of a 2-1. round- 
bottom flask and a fractionating column about 90 cm. long. 
When benzene no longer distils over, the distillation is continued 
in the same apparatus under reduced pressure, and the fraction 
that boils at g4~g6/2o mm. is collected. A small amount of 
dark-colored residue remains in the flask. The yield of almost 
colorless 0-tolunitrile is 300-330 g. (64-70 per cent of the theo- 
retical amount). 

^-Tolunitrile can be prepared in exactly the same manner 
from />-toluidine; the product, which distils at I04-io6/2o mm., 
solidifies in the receiver to a mass of nearly colorless needles 
which melt at 25-27. The yield is the same as with the ortho 
compound (Note 7). 



o-TOLUNITRILE AND />-TOLUNITRILE 71 

2, Notes 

1. If desired, the cuprous chloride may be suspended in 3 1. 
of water and the sodium cyanide added in the solid form. 

2. If several runs are to be made it may be more convenient 
to prepare a large quantity of cuprous cyanide solution, since 
this appears to be stable for several days. 

3. If the sodium nitrite is not of the highest technical purity 
it may be necessary to employ more than the indicated quantity. 
It is essential that the test for nitrous acid be permanent; if 
any unchanged amine remains, a precipitate of the diazoamino 
compound is formed on neutralization. A moderate excess of 
nitrite does not appear to interfere with the reaction, especially 
since the greater portion of the free nitrous acid is removed by 
the carbon dioxide liberated on neutralization. 

4. Sodium carbonate is preferable to sodium hydroxide 
because very little heat is evolved on neutralization. A slight 
excess of carbonate does not appear to be harmful. 

5. It is essential that the stirring be very vigorous. If the 
intermediate addition compound is allowed to collect on the 
surface of the liquid, it decomposes spontaneously with evolu- 
tion of much heat; this decomposition may take place with 
almost explosive violence. The presence of the benzene tends 
to diminish the viscosity of the intermediate product and permit 
it to be readily distributed throughout the mixture. Decom- 
position is quite rapid at o and is practically complete when 
room temperature is reached; it appears, however, to be advis- 
able to warm the mixture to 50, since if this be omitted the 
yield is slightly decreased. 

6. The apparatus described in Org. Syn. 2, 80, is suitable for 
the steam distillation. 

7. The product, as obtained in the above procedure, is of 
high purity; cresols do not appear to be formed under the con- 
ditions specified. The process has the advantage over that 
described in the literature l of giving rise to no poisonous fumes 
during the formation of the cuprous cyanide and during the 
interaction of this with the diazonium salt. The yield is prac- 
tically the same as in the older method. 



72 ORGANIC SYNTHESES 

3. Other Methods of Preparation 

The original method of Sandmeyer l prescribed the prepara- 
tion of the cuprous cyanide solution by dissolving copper sulfate 
in potassium cyanide solution and adding the strongly acid 
diazonium solution to it. Both of these operations involve the 
evolution of poisonous gases cyanogen in the first case and 
hydrogen cyanide in the second. Slight modifications have 
been subsequently suggested : the use of a 50 per cent excess of 
cuprous cyanide 2 and the heating of the cuprous cyanide solu- 
tion before the reaction. 3 

0-Tolunitrile has also been prepared from 0-toluidine by 
conversion into 0-tolyl isolhiocyanate and the boiling of this 
under a reflux condenser; 4 /?-tolunitrile has been prepared by 
distilling /?-toluic acid with potassium thiocyanate; 3 and a 
mixture of the two has been produced by the interaction of 
toluene, mercury fulminate, and aluminium chloride. 6 

1 Ber. 17, 2653 (1884); 18, 1492, 1496 (1885). 
2 Bcr. 19, 756 (1886). 
3 Ber. 23, 1026 (1890). 

4 Ber. 6, 419(1873). 

5 Ber 8,441 (1875). 

6 Ber. 36, 14 (1903). 




XXVI 
7>TOLUYL-o-BENZOIC ACID 



A1 2 C1,0 



Prepared by L F. FIKSER. 

Checked by ROGER ADAMS and R. L. SHRIXER. 

1. Procedure 

A 2-1. round-bottom flask is clamped to a ring-stand and 
equipped with a rubber stopper protected with tin foil and car- 
rying a glass stirrer with mercury seal and a reflux condenser. 
(Cf. Org. Syn. i, 4, Fig. i, a.) As an outlet for the hydrogen 
chloride, the top of the condenser is provided with a bent tube 
which almost touches the surface of the water in a half-rilled 
i-l. flask. 

One hundred grams of phthalic anhydride and 400 g. of 
toluene are placed in the flask, which is cooled in an ice bath 
while 200 g. of anhydrous aluminium chloride (Note i) is being 
ground to a fine powder. The chloride is now added all at once, 
and connections to the condenser made as rapidly as possible. 
Stirring is commenced at once and the ice bath is removed. 
The mixture warms up considerably and becomes olive-green 
in color. When the evolution of hydrogen chloride begins to 
slacken (ten minutes) a water bath is put into place and heated 
to 90 in the course of forty-five minutes. The temperature of 
the bath is kept at 90 and vigorous stirring continued for two 
and one-half hours. At this point, the evolution of hydrogen 
chloride will have practically ceased and the reaction will have 
been completed. The hot water in the bath is replaced first by 
cold water and then by ice, while stirring is continued. 

73 



74 ORGANIC SYNTHESES 

As soon as the flask is well cooled, it is disconnected and 
carried to the hood, and ice is slowly added, with shaking, until 
the dark mass is completely decomposed and the flask is about 
half filled with the mixture. After 150 cc. of crude concentrated 
hydrochloric acid has been added, the mass coagulates and the 
solution clears; the flask is then heated on the steam bath while 
preparations are being made for steam distillation. 

This operation, which removes the excess of toluene, may be 
carried out in the same flask and loss by transfer thus avoided 
(Note 2). The aqueous solution of aluminium chloride and 
hydrochloric acid, after thorough cooling, is decanted through a 
suction filter, the residue washed with a little cold water, and 
that collected on the filter returned to the flask. This residue 
consists almost solely of toluylbenzoic acid, partly crystalline, 
partly in oily lumps. 

A previously prepared and heated solution of 50 g. of sodium 
carbonate in i 1. of water is added, and steam is passed in to 
provide heat and agitation. With a rapid stream, the acid will 
go into solution in about ten minutes, leaving a small amount 
of brown, tarry material and a little alumina undissolved 
(Note 3). The solution is filtered while hot and transferred to a 
2-1. beaker, and the acid precipitated by the addition of 65 cc. 
of concentrated hydrochloric acid. The acid separates as an 
oil, which soon crystallizes. The solution is cooled in ice and 
the acid filtered and washed. 

The air-dried product is pure white and weighs 170 g. (Note 4). 
After drying at 100, the anhydrous acid melts at 138-139 and 
weighs 157 g. (96 per cent of the theoretical amount). Air-dried 
material is suitable for the condensation to ^-methyl anthra- 
quinone, p. 43. It may be recrystallized from toluene. 

2. Notes 

i. Although statements are found in the literature that 
quantitative yields may be obtained with smaller quantities of 
aluminium chloride, the ratio iCsH^CO^O : iAl 2 Clo is essen- 
tial. 



^-TOLUYL-o-BENZOIC ACID 75 

2. The steam distillation requires about fifteen minutes, and 
about 340-380 cc. of toluene is recovered. 

3. If, in extracting the acid with sodium carbonate, more 
than 2-3 g. of material remains undissolved, the residue is treated 
with dilute hydrochloric acid to remove alumina, washed, and 
again extracted with a little carbonate solution. This extract 
is neutralized separately since some tar may separate with the 
toluyl benzoic acid. In this event, it is filtered and extracted 
with cold carbonate solution, in which the tar is completely 
insoluble. 

4. According to Limpricht, the acid may Crystallize either 
in hydra ted or in the anhydrous condition, but the transition 
temperature is not stated. The loss of water upon drying at 
100 shows the compound obtained in this experiment to be the 
monohydrate. 

3. Other Methods of Preparation 

The only practical method for the preparation of ^-toluyl- 
0-benzoic acid is that proposed by Friedel and Crafts. 1 Limp- 
richt 2 has proposed a decrease in the quantity of aluminium 
chloride, but Heller and Schulke 3 and McMullen 4 have verified 
the importance of an excess of the condensing agent. 

1 Ann. chim. phys. (6) 14, 447 (1888). 

2 Ann. 299, 300 (1898;. 

3 Ber. 41, 3632 (1908). 

4 J Am Chem. Soc. 43, 1965 (1921). 



XXVII 
TRICARBALLYLIC ACID 



Prepared by H. T. CLARKE and T. F. MURRAY. 
Checked by C. S. MARVEL and M. M. BRUBAKER. 



1. Procedure 

IN a 3-1. flask, fitted with a stirrer and a fractionating column 
with condenser for downward distillation, are placed 912 g. of 
ethyl propane-i,i,2,3-tetracarboxylate (p. 29) and 950 cc. of a 
solution of equal volumes of pure concentrated hydrochloric acid 
and distilled water. A receiver with a side-tube is attached to 
the condenser; this side-tube leads to a water trap. The mix- 
ture is boiled, with continual stirring, at such a rate that the 
alcohol is removed as fast as it is formed, but without undue 
removal of water from the flask (Note i). The progress of the 
reaction can be followed by noting the rate at which carbon 
dioxide passes through the trap. When the temperature at the 
head of the column approaches 100, the flame is turned down 
so that very little liquid distils over. Heating is continued until 
evolution of carbon dioxide ceases (Note 2) . 

The flask is now disconnected from the stirrer and column, 
and the contents distilled off as completely as possible on the 
steam bath under reduced pressure. The remaining solid is 
freed from residual moisture and hydrochloric acid by allowing 
a slow current of dry air to pass over it, while still heating on the 
steam bath and maintaining a partial vacuum (Note 3). It is 
then redissolved in distilled water, and the solution filtered with 

77 



78 ORGANIC SYNTHESES 

the use of decolorizing carbon, and again evaporated under 
reduced pressure. 

The residue, when completely dry, is ground up, mixed to a 
paste with dry ether, filtered by suction, washed with dry ether 
and dried. The product so obtained (Note 4) is practically 
pure and melts at 160-161. The yield is 474-479 g. (95-96 per 
cent of the theoretical amount). 

2. Notes 

1. The temperature at the head of the column will give some 
idea of the relative amount of water passing over with the 
alcohol, but allowance must be made for the lowering of the 
distilling temperature by the carbon dioxide evolved. 

2. Twelve hours' heating is necessary to complete the reac- 
tion. 

3. The dry air is best introduced through a tube leading to 
the bottom of the flask; it is well not to disconnect the con- 
denser, but to note the point at which no more drops condense. 
The current of dry air should be quite slow not more than two 
bubbles per second in the sulfuric acid wash bottle. 

4. Tricarballylic acid is readily soluble in water (requiring 
about twice its weight at room temperature), but may, if 
desired, be recrystallized from it. Dry ether may also be 
employed, about 50 parts by weight being necessary. 

3. Other Methods of Preparation 

Tricarballylic acid was originally prepared by hydrolysis of 
the nitrile obtained from glycerol tribromohydrin and potassium 
cyanide; l it has also been obtained by the reduction of aconitic 
acid by sodium amalgam 2 or electrolytically. 3 The hydrolysis 
of ethyl propanetetracarboxylate may be carried out either in 
acid solution (with hydrochloric acid) 4 or in alkaline solution, 5 

1 Proc. Roy. Soc. 12, 237 (1862); Ann. 128, 352 (1863); Ann. 136, 272 (1865). 

2 Ann. 132, 62 (1864); Ber. 22, 2920 (1889); Ann. 314, 15 (1901). 

3 Compt. rend. 136, 1331 (1903). 

4 Ber. 24, 2889 (1891); Ann. 341, 102 (1905;. 

6 Ber. 23, 3760 (1890); J. prakt. Chem. (2) 45, 56 (1892). 



TRICARBALLYLIC ACID 79 

the former being the more convenient. Tricarballylic acid is 
also formed by the acid hydrolysis of the less accessible methyl 
propanepentacarboxylate and methyl propanehexacarboxylate, 7 
as well as by the alkaline hydrolysis of acetyl tricarballylic ester. 8 
Finally, it has been obtained by the oxidation of dkllylacetic 
ester with nitric acid 9 and of gallic acid with potassium chlorate 
and hydrochloric acid. 10 

Ber, 29, 1742 (1896); Ann. 347, 7 (1906). 
7 Ber. 29, 1279 (1896). 

8 Ann. 190, 324 (1878); Ber. 23, 3756 (1890). 

9 Ann. 201, 53 (1880). 
10 Ann. 177, 292 (1875). 



XXVIII 
TRIPHENYLMETHANE 

Alds - (C 6 H 5 ) 3 Ca-AlCl 3 +3HCl 

(C6H 5 ) 3 CC1-A1C1 3 +(C 2 H5) 2 - 

(C ri H 5 ) 3 CH+ CH 3 CHO + C 2 Hr,Cl + A1C1 3 

Prepared by J. F. NORRIS. 

Checked by H. T. CLARKE and T. F. MURRAY. 

1. Procedure 

To a mixture of 292 g. of dry benzene and 116 g. of dry 
carbon tetrachloride, (Note i) in a i-l. flask provided with a 
reflux condenser having a calcium chloride tube at its upper end, 
is added 100 g. of anhydrous aluminium chloride in lumps 
(Note 2). The flask is at once immersed in ice-water to within 
5 cm. of the top, and allowed to stand for twenty-four hours, 
the temperature of the water being allowed to rise to that of the 
room (Note 3). One hundred and ten grams of anhydrous ether 
is added in small portions, through the condenser, the flask being 
shaken occasionally during twenty minutes. The mixture is 
allowed to stand for twenty-four hours, and is then poured into 
a 5-!. flask containing 650 g. of ice and 25 cc. of concentrated 
hydrochloric acid. One liter of benzene is then added, and the 
mixture heated on a steam bath under a return condenser. 
After gently boiling for five to ten minutes, the mixture is allowed 
to cool to 40-50, when the benzene layer is separated, washed 
with 700 cc. of warm water containing 25 cc. of concentrated 
hydrochloric acid, and distilled. After the benzene has been 
removed under atmospheric pressure, the residue is transferred 
to a 300-cc. flask and distilled under reduced pressure, and a 

81 



82 ORGANIC SYNTHESES 

fraction boiling over the range 190-2 is/io mm. collected 
(Note 4). This weighs 135-160 g.; it solidifies on cooling. It 
is recrystallized from 550-650 cc. of ethyl alcohol (Note 5), and 
a colorless product, crystallizing in needles which melt sharply 
at 92, is obtained. This is filtered off and washed twice with 
3o-cc. portions of fresh alcohol. The alcoholic mother liquor is 
concentrated and the residue distilled under reduced pressure, 
material which distils over at i9o-2oo/io mm. being collected. 
This is recrystallized from ethyl alcohol, and 6-7 g. more of 
pure material is thus obtained. The total yield is 125-154 g. 
(68-84 per cent of the theoretical amount). 

2. Notes 

1. A convenient method for removing moisture from the 
carbon tetrachloride and the benzene consists in distilling off 
about one-tenth of the liquid; this first fraction contains all the 
moisture which may have been dissolved in the commercial 
products. It is, as a rule, unnecessary to distil the remaining 
liquid before use. 

2. The aluminium chloride may be a good grade of technical 
anhydrous material. If a powdered product be employed, the 
reaction is apt to proceed too rapidly. The lump material 
appears to be somewhat more efficient. 

3. With shorter periods of standing and lower temperatures, 
the yield falls off materially. Thus in one experiment in which 
the mixture was allowed to stand for twenty-four hours at 5-8, 
a large proportion of a lower-boiling product (apparently 
diphenylmethane) was formed, and only 109 g. of crude tri- 
phenylmethane was obtained. 

4. A dark, tarry residue amounting to 25-40 g. remains in 
the flask. 

5. Methyl alcohol may also be employed, but it is necessary 
to use 1600-1700 cc. of it. Triphenylmethane dissolves in one- 
third of its weight of warm benzene; it separates from this 
solution with benzene of crystallization, which is lost on exposure 
to air or recrystallization from alcohol. 



TRIPHENYLMETHANE 83 

3. Other Methods of Preparation 

The process here described consists essentially in the forma- 
tion of triphenylchloromethane by the interaction of carbon 
tetrachloride and benzene in the presence of aluminium chloride, 
and the reduction of this product by ether under the influence 
of the aluminium chloride present. 

Triphenylchloromethane is most satisfactorily prepared by 
the above method, 1 though ferric chloride may also be employed 
as a catalyst. 2 Its reduction by means of ether was first 
observed by Gomberg, 3 the catalyst in this case being zinc 
chloride; it had previously been shown 4 that triphenylchloro- 
methane (or triphenylcarbinol) is reduced to triphenylmethane 
by means of alcohol in the presence of sulfuric acid. 

Triphenylmethane has hitherto usually been prepared by 
the interaction of benzene and chloroform in the presence of 
aluminium chloride 5 or ferric chloride, 2 but the yields are con- 
siderably lower. Other methods consist in the action of benzal 
chloride upon benzene and aluminium chloride, 6 in heating 
benzal chloride and mercury diphenyl, 7 and in heating a mixture 
of benzaldehyde, benzene, and zinc chloride. 8 

ifier. 33, 3147 (1900). 
2 Ber. 32, 2422 (1899). 
3 J. Amer. Chem. Soc. 35, 204 (1913;. 
4 Ber. 45, 3188 (1912). 

5 Ber. 14, 1516 (1881); 26, 19^1 (1893); Bull. soc. chim. (2) 37, 6 (1882); 
Ann. 227, 108 (1885). 

6 Am Chem. J. 13, 556 (1891). 
7 Ber. 5, 906 (1872). 
s Ann. 242, 329 (1887). 



INDEX 



Absolute alcohol, IV, n, 29. (See also 

Ethyl alcohol.) 
Acetal, III, 1-2 

Acetaldehyde, III, i, gi, 92; IV, 53 
Acetamide, III, 3-5 
Acetanilide, IV, 40 
Acetic acid, II, 18, 33, 64; III, 3, n, 

455 IV, 5, 47 

Acetic anhydride, III, 21; IV, 35 
Acetone, I, 45-47, 53, 54, II, 41; HI, 

17,58,61; IV, 39 
Acetophenone, II, i 
Acetoxime, III, 62 
Acetylation, IV, i, 35, 40 
Acetyl chloride, IV, i 
Acetylene, IV, 23 
Acetyl mandelyl chloride, IV, 1-2 
Alkali fusion, III, 37 
Alkyl bromides, I, 1-13 
Alkylene bromides, I, i, 8, 9 
Allyl alcohol, I, 3, n, 15-19 
Allyl bromide, I, i, 3, n, 17 
Aluminium chloride, IV, 73, 8 1 
a-Aminocaproic acid, IV, 3-4 
i, 4-Aminonaphthol hydrochloride, III, 

7-10 

^-Aminophenylacetic acid, III, 11-12 
Ammonia, IV, 19 
Ammonium carbonate, II, 75; III, 3, 4; 

IV, 20 

Ammonium chloride, I, 75, 79, 81; III, 

67; IV, 47, 57 
Ammonium hydroxide, II, 37, 75; III, 

; IV, 3 

Ammonium sulfide, III, n 
iso-Amyl alcohol, I, 4, 10 
tso-Amyl bromide, I, i, 2, 4-5, 10 



Aniline, II, 71, 79; III, 7, 13; IV, 40 
Aniline arsenate, III, 13 
Aniline hydrochloride, III, 95 
Anthranilic acid, II, 47 
Arsanilic acid, III, 13-16 
Arsenation, IV, 5 

direct, III, 13; IV, 65 
Arsenic acid, III, 13, 14; IV, 65 
Arsenious oxide, IV, 5, 27 
Arsenoacetic acid, IV, 5-7 
Arsonoacetic acid, IV, 5-7 

B 

Barium arsonoacetate, IV, 5 
Barium chloride, IV, 5 
Barium hydroxide, I, 45, 46; IV, 66 
Benzalacetone, III, 17-19 
Benzalacetophenone, II, 1-3 
Benzaldehyde, I, 33; II, i, 5; III, 17 
Benzene, IV, 81 
Benzeneazo-a-naphthol, III, 8 
Benzenediazonium chloride, III, 7 
Benzenesulfonyl chloride, I, 21-23, 

7i, 72,81 

Benzil, I, 25- 27, 29, 30 
Benzilic acid, I, 29-32; III, 45 
Benzoic acid, I, 30; II, 5; III, 21 
Benzoic anhydride, III, 21-24 
Benzoin, I, 25, 26, 33-34 
Benzoquinone, II, 85-88; IV, 35 
Benzoyl acetate, III, 22 
Benzyl alcohol, II, 5 
Benzyl benzoate, II, 5-8 
Benzyl chloride, II, 9; IV, 59 
Benzyl cyanide, II, 9-11, 27, 57, 63 
Borax, IV, 46 

Bromine, I, 2, 3, 35, 39; III, 41; IV, 9 
Bromine in glycerol, IV, 14, 38 



86 



INDEX 



a-Bromo-w-caproic acid, IV, 3, 9-10 
<x-Bromonaphthalene, I, 35-37 
0-Bromophenol, I, 40, 41 
/>-Bromophenol, I, 39-43 
0-Bromopropionic acid, III, 25-26, 51 
Bromostyrene, II, 67 
n-Butyl alcohol, I, 5, 6; III, 69 
w-Butyl bromide, I, 2, 5-6, 10; IV, n 
-Butylmalonic ester (ethyl), IV, 11-12 
n-Butyl nitrite, IV, 19-20 

C 

Calcium chloride, III, i, 34, 84, 92 

Calcium oxide, IV, 53 

Calomel, III, 100 

w-Caproic acid, IV, 9 

Capryl alcohol. (See Methyl hexyl car- 

binol.) 

Carbanilide, III, 95 
Carbon disulfide, I, 39, 41 
Carbontetrachloride, I, 17, 67-70; II, 

23; III, 25, 41, 51, 76; IV, 29, 81 
Castor oil, I, 61, 63, 65 
Catechol, III, 27-82 
Chlorine, II, 37 

Chloroacetic acid, III, 53, 83; IV, 5 
Chlorobenzene, I, 21 
Chloroform, I, 81; 111,68; IV, 37 
0-Chloromercuriphenol, IV, 13-14, 37 
/>-Chloromercuriphenol, IV, 13 
0-Chlorotoluene, III, 33-35 
/>-Chlorotoluene, III, 34 
Congo Red, III, 15, 61 
Copper sulfate, II, 38; III, 33, 79 
Corn cobs, I, 49, 51 
Coupling Reaction, II, 47; III, 7 
Creatine, IV, 15 
Creatinine, IV, 15-17 
Creatinine picrate, IV, 16 
Creatinine zinc chloride, IV, 15 
/>-Cresol, III, 37-39 
Cupferron, IV, 19-21 
Cuprous chloride, III, 33, 34, 79; IV, 69 
Cuprous cyanide, IV, 69 

D 

Decarboxylation, II, 93 
Dehydration, I, 53, 67; III, 3, 21; IV, 
IS 



Diacetone alcohol, I, 45-47, 53, 54 

Diagrams : 

Acetylene condensation, IV, 24 
Automatic extraction, III, 88 
Automatic separation, I, 64, 68; 

II, 23; III, 29 

Concentration of liquids, IV, 54 
Condensation of low-boiling liquids, I, 

76 

Dehydration with solvent, II, 23 
Distillation flask and column, I, 40 
Extraction and crystallization, II, 49; 

III, 88 

Hopper, III, 47 
Manipulation of gases, IV, 24 
Mechanical stirrcr, I, 4, 12; III, 29 
Mercury seal, I, 4 

Pyrogenic decomposition, IV, 40 
Rapid evaporation, IV, 54 
Steam distillations, I, 50; II, 80 

Diazotization, II, 47, 71, 80; III, 7, 9, 
33, 79,87,89; IV, 69 

Dibenzalacetone, III, 18 

Dibenzyl ether, II, 6 

9, lo-Dibromoanthracene, III, 41-43 

1, 4-Dibromonaphthalene, I, 35, 36 

2, 4-Dibromophenol, T, 40 

a, 7-Dichloroacetone, II, 13-15 
Diethyl malonate, IV, n, 27, 29 
Dihydroxymethylbenzopyrone. (See /3- 

Methyl esculetin.) 
Dimethylamine hydrochloride, I, 81; 

III, 68 
/>-Dimethylaminobenzaldehycie, II, 17- 

21 

Dimethylaniline, II, 17, 47 
Diphenylacetic acid, III, 45-46 
Diphenylurea, III, 95 
Disodium phosphate, IV, 50 
Di-/>-tolylethane (unsym), IV, 23-25 

E 

Epichlorohydrin, III, 47-49 
Esterification, III, 51, 53; II, 23, 27 
Ether. (See Ethyl ether ) 
Ethyl acetate, III, 96 
Ethyl acetoacetate, IV, 45 



INDEX 



Ethyl alcohol, 1, 6; II, 23, 27; III, 1,51, 

54, 68, 69, 91; IV, n, 29 
Ethyl bromide, I, i, 6-7 
Ethyl /3-bromopropionate, III, 51-52 
Ethyl cyanoacetate, III, 53-56 
Ethylene chlorohydrin, III, 57 
Ethyl ether, III, 47, 48; IV, 59, 81 
Ethyl fumarate, IV, 29 
Ethyl hydracrylate, III, 52 
Ethyl malonate, IV, n, 27, 29 
Ethyl mesoxalate, IV, 27 
Ethyl oxalate, II, 23-26 
Ethyl oxomalonate, IV, 27 -28 
Ethyl phcnylacetate, II, 27-28 
Ethyl propanc-i, i, 2, 3-tetracarboxyl- 

ate, IV, 29 30, 77 
Ethyl sulfate, IV, 60 
Extraction, II, 49; III, 88 



Fehling's solution, I, 26 
Ferrous sulfate, II, 79 
Ferrous sulfide, III, 12 
Formaldehyde, II, 17; 111,67; IV, 47, 

53 

Formic acid, I, 15 18 
Friedel and Crafts' Reaction, IV, 73, 81 
Furfural, I, 49-52 

G 

Gelatine, II, 37 

Glycerol, I, 15, 17; II, 29, 33, 79 

Glycerol , 7-dichlorohydrin, II, 29-31, 

III, 47 

Glycerol a-monochlorohydrin, II, 33-35 
Glycine, IV, 31-33 
Grignard Reaction, IV, 59 
Guaiacol, III, 28 

H 

Hydrazine sulfate, II, 37-40 
Hydrobromic acid, I, i, 2-3, 4-11, 36, 

39; III, 25, 28, 43; IV, 31 
a-Hydroformaminc cyanide, IV, 47 
Hydrogen peroxide, III, 27 
Hydrogen sulfide, III, u 
Hydrolysis, II, 27, 59, 63; III, 25, 53; 

IV, 31, 77 



Hydroquinone, II, 85 
Hydroxyhydroquinone triacetate, IV, 

35-36, 45 
Hydroxylamine hydrochloride, III, 61- 

64 

I 

Imide formation, II, 75 
lodination, IV, 37 
Iodine, I, 53, 54; III, 45; IV, 37 
lodoform, I, 57, 58 
0-Iodophenol, IV, 37-38 



K 



Ketene, IV, 39-42 



Lauryl alcohol, I, 7 
Lauryl bromide, I, 7 

M 

Magnesium, IV, 59 
Malonic ester synthesis, IV, n, 29 
Mandelic acid, IV, i 
Mercuration, III, 65, 99; IV, 13 
Mercuric acetate, IV, 13 
Mercuric chloride, III, 99 
Mercuric iodide, IV, 37 
Mercuric sulfate, IV, 23 
Mercurous chloride, HI, 100 
Mercury di-/>-tolyl, III, 65-66 
Mesitylene, II, 41-45 
Mesityl oxide, I, 53~55 
Methylal, III, 67, 69 
Methyl alcohol, III, 29, 71; IV, 3, 16, 

3i 
Methylamine hydrochloride, I, 81; III, 

67-70 

0-Methyl anthraquinone, IV, 43-44 
Methyl benzoate, III, 71, 72 
Methyl bromide, III, 29 
Methylene aminoacetonitrile, IV, 31, 

47-48 

Methylene iodide, I, 57-59 
^-Methyl esculetin, IV, 45-46 
Methyl formate, III, 67 
Methyl hexyl carbinol, I, 61-66 
Methyl iodide, I, 57, 59 
Methyl o-nitrobenzoate, III, 72 



88 



INDEX 



Methyl w-nitrobenzoate, III, 71-72, 73 
Methyl Red, II, 47-61 

N 

Naphthalene, I, 35, 36 
a-Naphthol, III, 7, 9 
/3-Naphthoi, II, 6 1 
Nicotine, IV, 49 
Nicotinic acid, IV, 49-51 
Nitration, II, 57; III, 71 
Nitric acid, I, 25, 26; II, 57; III, 71; 

IV, 27, 49 

3-Nitro-4-aminotoluene, III, 91 
;-Nitroaniline, III, 79, 87 
Nitrobenzene, II, 79; IV, 19, 57 
;w-Nitrobenzoic acid, III, 73-74 
/>-Nitrobenzoic acid, II, 53-55; III, 75, 

76 

/>-Nitrobenzoyl chloride, III, 75-77 
/>-Nitrobenzyl cyanide, II, 57-58, 59 
w-Nitrochlorobenzene, III, 79-81 
Nitromethane, III, 83-85 
w-Nitrophenol, III, 87 
^-Nitrophenylacetic acid, II, 69-60, III, 

ii 

Nitrosation, II, 17, 61; IV, 19 
/>-Nitrosodimethylanilinehydrochloride, 

II,i7 

Nitroso-/3-naphthol 7 II, 61-62 
Nitroso-/3-phenylhydroxylamine, IV, 21 
w-Nitrotoluene, III, 91-93 
/>-Nitrotoluene, II, 53 
w-Nitro-^-toluidine, III, 91 
Nitrous anhydride, IV, 27 

O 

w-Octyl alcohol, I, 7 

w-Octyl bromide, I, 7 

Oxalic acid, I, 17, 18; II, 23 

Oxalic acid ^anhydrous), I, 18, 67-70 



Paraformaldehyde, I, 75, 79, 81 
Pentaerythritol, IV, 53-56 
Phenol, II, 39; IV, 13, 65 
Phenol burns, IV, 14 
Phenolphthalein, III, 83 
Phenolsulfonic acid, III, 51 



Phenylacetic acid, II, 10, 63-6$ 
Phenylacetylene, II, 67-69 
Phenylhydrazine, II, 71-74 
0-Phenylhydroxylamine, IV, 19, 67-68 
Phenylurea, III, 95-97 
Phosphoric acid, III, 21 
Phosphorus, III, 45 
Phosphorus oxychloride, I, 22; III, 75 
Phosphorus pentachloride, I, 21, 22; 

HI, 75, 76 

Phosphorus trichloride, IV, 9 
Phthalic anhydride, II, 75; IV, 43, 73 
Phthalimide, II, 75-77 
Picric acid, IV, 16 
Potassium acid sulfate, IV, 63 
Potassium hydroxide, I, 29; II, 67; III, 

37 

Potassium iodide, IV, 37 
w-Propylbenzene, IV, 69-61 
Propylene bromide, I, 3, 11 
Pyridine, IV, 31 

Pyrogenic decomposition, IV, 39 
Pyruvic acid, IV, 63-64 



Quinoline, II, 79-83 
Quinone, II, 86-88 



Salicylaldehyde, III, 27 

Salting-out, IV, 57 

Saponification, III, 73 

Sodium acetate, II, 48 

Sodium alcoholate, IV, 11 

Sodium arsenite, I, 57, 58; IV, 5 

Sodium arsonoacetate, IV, 6 

Sodium benzenesulfonate, I, 21, 22 

Sodium benzylate, II, 6 

Sodium bisulfite, I, 62, 63; III, 33, 45, 

61, 79 

Sodium bromide, I, 2, 6, 8, 10 
Sodium chloride, IV, 13 
Sodium cyanide, I, 33; II, 9; III, 53, 

57; IV, 47, 69 

Sodium dichromate, II, 13, 53, 85, 95 
Sodium formate, III, 69 
Sodium hydrosulfite, III, 8, 10 



INDEX 



89 



Sodium ^-hydroxyphenylarsonate, IV, 

65-68 

Sodium hypophosphite, IV, 6 
Sodium iodide, III, 65 
Sodium, metallic, II, 5, 42; IV, n, 29 
Sodium nitrite, II, 17, 47, 61, 71, 80; 

111,7,33,61,79,83,87,91; IV, 69 
Sodium sulfite, II, 71; III, 33 
Sodium ^-toluenesulfinate, II, 89-91; 

III, 99 

Sodium />-toluenesulfonate, III, 37, 38 
Sulfosalicylic acid, III, 51 
Sulfur dioxide, II, 71; III, 9, 61 
Sulfuric acid, fuming, IV, 43 



Tartaric acid, I, 46; IV, 63 
Tetrabromophenolsulfonphthalein, III, 

14 
Tetra-hydroxymethylmethane, IV, 53- 

56 

Thionyl chloride, IV, i 
Thiophenol, I, 71-74 
Toluene, II, 48; III, 27, 30, 42; IV, 

23, 73 

/>-Toluenesulfonyl chloride, II, 89 
0-Toluidine, irt, 33; IV, 69 



^-Toluidine, III, 34; IV, 70 
o-Tolunitrile, IV, 69-72 
/>-Tolunitrile, IV, 69-72 
/>-Tolyl-0-benzoic acid, IV, 43, 73-75 
/>-Tolylmercuric chloride, III, 85, 99- 

100 

Tricarballylic acid, IV, 77-79 
Trimethylamine, I, 75-78 
Trimethylamine hydrochloride, I, 75, 

79-82 

Trimethylene bromide, I, 2, 8, 10, n 
Trimethylene bromohydrin, I, n 
Trimethylene glycol, I, 8 

1, 3, 5-Trinitrobenzene, II, 93-94, 96 

2, 4, 6-Trinitrobenzoic acid, IT, 93, 95- 

97 

2, 4, 6-Trinitrotoluene, II, 93, 95 
Triphenylmethane, IV, 81-83 



U 



Urea, III, 95 



X 



Xylene, III, 65, 99 



Zinc chloride, IV, 15 

Zinc dust, I, 71, 72; II, 89, IV, 57